Hongmei Shao; Junjie Chen
Abstract
Background: Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. In this study, we investigated the effectiveness ...
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Background: Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood. In this study, we investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis.Methods: To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-γ, IL-17, TNF-α, IL-23, IL-6, IL-1β, TGF-β, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques.Results: The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-γ, IL-17, TNF-α, IL-23, IL-6, and IL-1β were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-β, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice.Conclusion: EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.
Rouhollah Hemmati Bushehri; Mahmoud Reza Jaafari; Ghasem Mosayebi; Ali Ghazavi; Ali Ganji
Abstract
Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack ...
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Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack of immunogenicity and toxicity, making them ideal for delivering various drugs.Objective: To prepare liposomes (HSPC/Chol/mPEG2000-DSPE) containing rosemary alcoholic extract (LipRos) and evaluate its antitumor properties in a mouse model of colorectal cancer (CRC).Methods: LipRos were prepared and characterized. CRC was induced in Balb/c mice by subcutaneous injection of C26 cells, and tumor size was monitored continuously. The MTT assay was performed to evaluate cytotoxicity, and liver and kidney function tests were conducted to assess safety. The expression of the pro-apoptotic gene B-cell-lymphoma-2 (Bcl-2), the anti-apoptotic gene Bcl-2-associated-X-protein (Bax), and the expression of cytokines Tumor-necrosis-factor-alpha (TNF-α), Transforming-growth-factor-beta (TGF-β), and Interferon-gamma (IFN-γ) were investigated using real-time PCR. Flow cytometry was used to evaluate the count of cytotoxic (CTL) and regulatory T lymphocytes (Tregs) in spleen and tumor tissue.Results: The results showed that the size of liposomal formulations and their encapsulation efficiency were 113.4 nm and 85%, respectively. The MTT assay demonstrated insignificant cytotoxicity of LipRos on splenocytes, and the tumor size was significantly reduced in the LipRos group (P=0.00045). LipRos also significantly decreased Bcl-2 gene expression (P=0.0086), increased Bax and IFN-γ gene expression (P=0.031), and enhanced the infiltration of CTLs in tumor tissue (P=0.023).Conclusions: This study showed that PEGylated (Poly-Ethylene-Glycol) liposomes containing rosemary extract exhibit an antitumor effect on C26 colorectal cancer cells through multiple mechanisms. These findings can be utilized in future studies.
Anil Demir; Husnu Sevik; Mert Guler; Furkan Turkoglu; Coskun Cakir; Mert Mahsuni Sevinc; Erdem Kinaci; Ufuk Oguz Idiz
Abstract
Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies ...
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Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.Objective: To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment.Methods: Patients with stage 1-2 breast cancer and healthy volunteers were included in the study. The breast cancer patients were classified as luminal A, luminal B, and triple negative based on ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants. Age, menopausal status, and hematologic parameters were also compared between groups.Results: The study involved 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients than in healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients showing lower cytokine levels, except for MCP-1.Conclusion: The decreased levels of cytokines in triple-negative breast cancer indicate lower immunogenicity leading to more aggressive tumor progression as a result of an insufficient immune response.
Guizhen Lin; Lei Zhang; Zheng Yan; Wei Jiang; Beibei Wu; Xiaofang Xiong
Abstract
Background: CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood.Objective: To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 ...
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Background: CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood.Objective: To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 (IL-17)-producing CD8+ T (Tc17) cells.Methods: Apolipoprotein E-deficient mice were fed a high-fat diet to induce atherosclerosis. Flow cytometry was used to identify and isolate aortic CD8+ T cell subsets, which were then cultured in vitro to assess their pro-inflammatory activities. The cholesterol content of the CD8+ T cell subsets was quantified.Results: T-box expressed in T cells (T-bet)+ Tc1 cells and retinoic acid-related orphan receptor gamma t (RORγt)+ Tc17 cells were found in the atherosclerotic aorta. Aortic CD8+ T cells showed lower pro-inflammatory activity compared to splenic counterparts, with less interferon-gamma (IFN-γ) (P <0.01) and tumor necrosis factor-alpha (TNF-α) production (P <0.01). Surprisingly, aortic CD8+ T cells expressed little IL-17 and interleukin-21 (IL-21) despite the presence of Tc17 cells. Aortic Tc1 and Tc17 cells expressed high levels of 2B4 and programmed cell death protein 1 (PD-1). Furthermore, aortic Tc1 and Tc17 cells had higher cholesterol contents than splenic CD8+ T cells (P <0.05, respectively). Cholesterol treatment decreased IFN-γ expression in Tc1 cells (P <0.001) and reduced IL-17 expression in Tc17 cells (P <0.001). Additionally, cholesterol up-regulated 2B4 and PD-1 on Tc1 (P <0.001) and Tc17 cells (P <0.001).Conclusion: Aortic CD8+ T cells, particularly aortic Tc17 cells, are functionally exhausted in atherosclerosis, possibly due to the influence of cholesterol.
Adamu Imam Isa
Abstract
Background: Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, ...
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Background: Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, based on their traditional use in treating inflammation.Objective: To investigate the inhibitory effects of methanol leaf extracts from selected plants on enzymes involved in chronic inflammation.Methods: The inhibition of nitric oxide production, acetylcholinesterase activity, and 15-lipoxygenase activity was assessed using the Griess reagent method, Ellman’s colorimetric method, and the ferrous oxidation-xylenol orange assay. The quantity of M1/M2 cytokines released was quantified using a flow cytometerResults: At a concentration of 50 µg/mL, the methanol extracts of P. limbata exhibited the highest NO inhibition (97.67%), followed by P. nepalensis (93.06%) and P. setosula (92.78%). The NO inhibition caused by the plant extracts was correlated directly with the decrease in NO release by the LPS-stimulated macrophages. Furthermore, the pro-inflammatory enzyme assays indicated that the methanol extracts of P. setosula exhibited the highest enzyme inhibitory activity (LOX 89.59%, AChE 72.12 %). This was followed by P. limbata (with 92.76% for LOX and 56.93% for AChE) and P. nepalensis (with 88.16% for LOX and 47.17% for AChE). Cytokine assays revealed that the extracts of P. limbata had significant dose-dependent suppressive effects on IFN-γ and TNF-α expression while promoting the secretion of IL-2, IL-4, IL-6, and IL-10.Conclusion: Extracts of P. limbata contain immunomodulatory compounds that could be further explored as potential remedies to target the molecular drivers of chronic inflammation.
Fatemeh Kamankesh; Ali Ganji; Ali Ghazavi; Ghasem Mosayebi
Abstract
Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.Objective: To investigate ginger extract’s effect on reducing inflammation and improving the symptoms ...
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Background: Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.Objective: To investigate ginger extract’s effect on reducing inflammation and improving the symptoms in the EAE model.Methods: The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation.Results: The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups.Conclusion: The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.
Jing Sun; Jiabao Zhao; Chao Sun; Yu ting Zhu; Ping Zhou; Shu xian Gao; Ying-Ao Fan; Hao-Yuan Jiang; Qing-Wei Zheng; Jun-Chang Guan
Abstract
Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression ...
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Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. Methods: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. Results: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. Conclusion: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.
Zeinab Amirkhani; Mehrosadat Alavi; Mehdi Kalani; Ali Alavianmehr; Shirin Farjadian
Abstract
Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid ...
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Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer (DTC). Methods: A total of 85 patients with DTC were allocated into two groups based on RAI dosage after thyroidectomy. Patients in each group were randomly distributed into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Fifteen healthy individuals were included as controls. Serum cytokine levels including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, TNF-α and IFN-γ were determined by cytometric bead assay. Results: IL-4, IL-6, IL-21 and IL-22 levels in patients with DTC were higher than in the healthy controls. Regardless of RAI dosage, IL-6 showed an increasing trend after RAI ablation. IL-4, IL-22, and IL-17A remained at considerably higher levels than in the healthy controls after RAI ablation. Within-group comparisons showed a significant reduction in Th1+Th17/Th2+Th22 ratio in G2 patients 1 week after RAI ablation. Between-group comparisons showed increased IL-10 levels in G3 compared with G1 patients one week after high-dose RAI ablation. In G3, Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were remarkably lesser than in G2 patients 1 month after intermediate-dose RAI ablation. Conclusion: Our results showed better anti-inflammatory effects of omega-3 when it was used therapeutically after RAI ablation in patients with DTC than when it was used prophylactically before RAI.
Wei Li; Lin Li; Lin He; Yun Du; Hai-Dong Fu; Zhao-Yang Peng; Wen-Qing Xiang; Jian-Hua Mao
Abstract
Background: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). Objectives: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. Methods: 182 children with INS and 100 healthy ...
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Background: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). Objectives: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. Methods: 182 children with INS and 100 healthy controls were enrolled in this study. Blood genomic DNAs were used to analyze20 single nucleotide polymorphisms (SNPs) in 8 cytokine genes includingIL-21, IL-18, IL-6, IFN-γ, IL-4, IL-10, IL-17F, IL-17A d by multi-PCR with next-generation sequencing. Results: Among 182 children with INS, 89 (48.6%) were steroid-sensitive (SS), 73 (39.9%) were steroid-dependent (SD) and 21 (11.5%) were steroid-resistant (SR). In 20 SNPs, IL-4-rs2243283 exhibited a significantly different genotype distribution between INS and the healthy controls (CC is a risk genotype: 66.5% of INS VS 51% of the control; OR=1.91, p=0.012). Patients carrying AG genotype (rs2275913, IL-17A) had a significantly higher risk of steroid-dependent response (69.1% of SD VS 46.4% of SS; OR=2.58, p=0.014). Similarly, patients carrying A allele of IL-10-rs1800872 (39.0% of SD VS 26.7% of SS; OR=1.76, p=0.018) and C allele of IL-10-rs1800896 (12.3% of SD VS 3.9% of SS; OR=3.44, p=0.004) had a higher risk of steroid-dependent response. However, none of these 20 SNPs showed a significant difference between SS group and SR group. Conclusion: Among the 20 cytokine gene SNPs, IL-4-rs2243283 might increase the susceptibility to INS in Chinese children; rs2275913 of IL-17A, rs1180972, and rs1800896 of IL-10 show association with the steroid -response in Chinese INS children.
German Reynaldo Jiménez-Gastélum; Arely Monserrant Espinoza-Ortega; Rosalío Ramos-Payán; Maribel Aguilar-Medina; Jorge López-Gutiérrez; Carlos Villegas-Mercado; Luis Antonio Ochoa-Ramirez; Horacio Rendón-Aguilar; Juan Fidel Osuna-Ramos; Juan José Ríos-Tostado; Jesús Salvador Velarde-Félix
Abstract
Background: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. Objective: To determine the association of serum cytokine ...
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Background: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. Objective: To determine the association of serum cytokine levels with COVID-19 severity. Methods: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. Results: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. Conclusion: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.
Huimin Yan; Xinyu Zhang; Ying Lv
Monireh Zare; Behnaz Valipour; Seyede Momeneh Mohammadi; Mohammad Nouri; Aliakbar Movassaghpour; Hojjatollah Nozad Charoudeh
Volume 14, Issue 3 , September 2017, , Pages 192-199
Abstract
Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, ...
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Background: The mammalian target of rapamycin (mTOR) is important in hematopoiesis. Despite the central role of mTOR in regulating the differentiation of immune cells, the effect of mTOR function on cord blood mononuclear cells is yet to be defined. Objectives: To evaluate the effect of mTOR inhibition, using rapamycin on the proliferation and apoptosis of cord blood mononuclear cells, as well as on the B and T cell expansion. Methods: Cord blood mononuclear cells were cultured in the presence of IL-2, IL-7 and IL-15 cytokines and inhibited by rapamycin for 14 days. The harvested cells were evaluated at distinct time points by flow cytometry. Results: The mTOR expression decreased in the presence of rapamycin on day 14. Inhibition of mTOR reduced the proliferation of the cord blood mononuclear cells, yet did not influence apoptosis. Moreover, the number of T and NK cells was significantly reduced in the presence of rapamycin, while no change was observed in the B cell expansion. Conclusion: mTOR signaling plays a crucial part in cord blood derived NK and T cells expansion.
Reza Feyzi; Mohammad Hossein Boskabady; Seyedeh Masoumeh Seyed hosseini Tamijani; Houshang Rafatpanah; Seyed Abdolrahim Rezaei
Volume 13, Issue 4 , December 2016, , Pages 263-273
Abstract
Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and ...
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Background: Several biological and medical benefits of Saffron, Crocus sativus
(Iridaceae), have been demonstrated. However, mechanisms of actions for purified
constituents are greatly unknown. Objective: To examine the effects of Safranal, a main
constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood
mononuclear cells (PBMC) were examined. Methods: Effects of Safranal at 0.1, 0.5
and 1 mM concentrations were evaluated on cell viability and production of interleukin
4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin
(PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline. Results: In
stimulated cells, different concentrations of Safranal caused significant decrease of
lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal
inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, high
concentration of Safranal significantly decreased cell viability of non-stimulated
PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than
dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in
non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal
concentrations both in non-stimulated and stimulated cells were significantly higher
than those of control and PHA stimulated groups, respectively (p<0.05). Conclusion:
The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on
Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory
diseases associated with Th1/Th2 imbalance.
Henu Kumar Verma; Aditya Nath Jha; Prafulla Kumar khodiar; Pradeep Kumar Patra; Lakkakula Venkata Kameswara Subrahmanya Bhaskar
Volume 13, Issue 2 , June 2016, , Pages 124-131
Abstract
Background: Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases. ...
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Background: Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases. Intron-3 of interleukin-4 gene (IL-4) harbors 70-bp variable number of tandem repeats (VNTR) that may alter the expression level of IL-4 gene. Objective: To determine the distribution of IL-4 70-bp VNTR polymorphism in seven genetically heterogeneous populations of Chhattisgarh, India and their comparison with the finding of other Indian and world populations. Methods: A total of 371 healthy unrelated individuals from 5 caste and 2 tribal populations were included in the present study. The IL-4 70-bp VNTR genotyping was carried out using PCR and electrophoresis. Results: Overall, 3 alleles of IL-4 70-bp VNTR (a2, a3 and a4) were detected. The results demonstrated the variability of the IL-4 70-bp VNTR polymorphism in Chhattisgarh populations. Allele a3 was the most common allele at the 70-bp VNTR locus in all populations followed by a2 allele. This study reports the presence four repeat allele a4 at a low frequency in the majority of the Chhattisgarh populations studied. Further, the frequency of the minor allele (a2) in Chhattisgarh populations showed similarity with the frequencies of European populations but not with the East Asian populations where the a2 allele is a major allele. Conclusions: Our study provides a baseline for future research into the role of the IL-4 locus in diseases linked to inflammation in Indian populations.
Zeynab Aliyari; Forogh Alemi; Balal Brazvan; Hamid Tayefi Nasrabadi; Hojjatollah Nozad Charoudeh
Volume 12, Issue 1 , March 2015, , Pages 16-26
Abstract
Background: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell transplantation (HSCT), used in Leukemia treatment. CD26+ cells, a fraction of CD34 positive cells, are a major population of UCB cells which negatively regulate the in vivo homing and engraftment of HSCs. CD26 ...
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Background: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell transplantation (HSCT), used in Leukemia treatment. CD26+ cells, a fraction of CD34 positive cells, are a major population of UCB cells which negatively regulate the in vivo homing and engraftment of HSCs. CD26 is highly expressed in various cells such as HSCs, immune cells, fibroblasts, and epithelial cells. It has been shown that the inhibition of the CD26 on CD34+ cells improves the efficiency of Hematopoietic Stem and Progenitor Cell (HPC) transplantation. Objective: To evaluate the relationship between the production of B, T, and NK cells from the CD26 positive fraction of cord blood mononuclear cells. Methods: Cord blood mononuclear cells were cultured for 21 days using different combinations of stem cell factors (SCF), Flt3 ligand (FL), IL-2, IL- 7, and IL-15. The harvested cells were then analyzed by flowcytometry every week for 21 days. Results: T cell differentiation from CD26 subset of cord blood mononuclear cells increased by using IL-2 and IL-7. Our data showed that IL-2 and IL-7 significantly affected the generation of B cells from CD26 positive cord blood mononuclear cells. On the other hand, NK (NKp46+) derived CD26+ cells increased by IL-15 and IL-2. Conclusion: Taking all into account, we conclude that B, T, and NK cells can differentiate from the CD26+ subset of mononuclear cord blood cells by using key regulatory cytokines.
Feryal Dabagh-Gorjani; Fahimeh Anvari; Jaleh Zolghadri; Eskandar KamaliSarvestani; Behrouz Gharesi-Fard
Volume 11, Issue 4 , December 2014, , Pages 233-245
Abstract
Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. ...
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Background: Preeclampsia (PE) is one of the most complex and life-threatening pregnancy disorders and is considered as a major cause of mortality among mothers and fetuses worldwide. Although the exact etiology of PE is not well known several lines of evidence support an immunological etiology for PE. Objective: To investigate the differences in the expression of TLRs 2, 4, 5, and 6 and a group of inflammatory cytokines including IL-1, IL-6, TNF-α and IFN-γ in placentas from PE and healthy pregnant women in their third trimester of pregnancy. Methods: This case-control study was performed on fifteen PE and fifteen age and gestational matched healthy pregnant women in the third trimester of pregnancy. Real time PCR (RT-PCR) technique was used to determine the expression of TLRs 2, 4, 5, and 6 in the maternal and fetal parts of the placenta. Moreover, the expressions of IL-1, IL-6, TNF-α and IFN-γ at RNA level in placental samples, peripheral, and cord blood were investigated. Results: The results of the present study indicated that the expressions of TLRs 4, 5 and 6 were significantly increased in both maternal part (p<0.001 and p<0.003 for TLRs 4, 6 and TLR 5, respectively) and fetal part (p<0.001), while TLR2 showed significant increase only in the fetal part of PE placentas (p<0.002). The levels of all studied cytokines showed over-expression within peripheral and cord blood samples from PE patients (p<0.001 for IL-1, IL-6, and IFN-γ and p<0.004 for TNF-α in both cord and peripheral blood samples). Conclusion: The finding of the present study indicated that the expression of the studied TLRs and inflammatory cytokines are generally suppressed in normal pregnancy, but are up regulated in preeclamptic women. Moreover, it seems that the maternal and fetal parts of the placenta may play different roles in the induction of the inflammatory status within the placenta.
Mete Eyigor; Hulya Eyigor; Ustun Osma; MustafaDeniz Yilmaz; Nuray Erin; Omer Tarik Selcuk; Cem Sezer; Meral Gultekin; Sadi Koksoy
Volume 11, Issue 4 , December 2014, , Pages 259-268
Abstract
Background: Although the imbalance of cytokines in Head and Neck Squamous Cell Carcinoma (HNSCC) is well known, there is scarce data regarding its occurrence during dysplasia, before the malignant transformation. Objective: To determine whether laryngeal dysplasia patients show a different cytokine profile ...
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Background: Although the imbalance of cytokines in Head and Neck Squamous Cell Carcinoma (HNSCC) is well known, there is scarce data regarding its occurrence during dysplasia, before the malignant transformation. Objective: To determine whether laryngeal dysplasia patients show a different cytokine profile than patients with cancer and healthy controls. Methods: Seventeen newly diagnosed, untreated larynx squamous cell carcinoma (SCC) and six laryngeal dysplasia patients as well as 22 healthy controls were analyzed for circulating cytokines. A flowcytometry Th1/Th2 cytokine array kit was used to quantitatively measure Interleukin-2 (IL-2), IL-4, IL-6, IL-10, Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ) levels. Additionally, IL-8 levels were determined through ELISA. Results: IL-6, IL-8 and IL-10 were determined to be statistically increased in SCC patients (p<0.05). IL-8 and IL-10 levels were also higher in SCC patients than dysplasia patients (p<0.05). Additionally, IL-6 and IL-10 were all found to be markedly increased in dysplasia patients compared with controls (p<0.05). Conclusion: Our results demonstrate an imbalance of IL-6 and IL-10 not only in HNSCC but also in laryngeal dysplasia.
Motahareh Bahadori; Saeed Zarei; Amir Hassan Zarnani; Omid Zarei; Farah Idali; Reza Hadavi; Mahmood Jeddi-Tehrani
Volume 11, Issue 2 , June 2014, , Pages 97-104
Abstract
Background: Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). Objective: To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 ...
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Background: Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). Objective: To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women. Method: Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls. Results: The frequencies of IL- 10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls. Conclusion: These results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.
Nadeem Afzal; Shakeela Zaman; Aneela Asghar; Khursheed Javed; Faheem Shahzad; Abu Zafar; Abdul Hanan Nagi
Volume 11, Issue 1 , March 2014, , Pages 40-48
Abstract
Background: Diabetes mellitus (DM) is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. Objective: To determine serum IL-6 and IL-17 of type 2 diabetes mellitus (T2DM) patients with retinopathy. Methods: ...
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Background: Diabetes mellitus (DM) is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. Objective: To determine serum IL-6 and IL-17 of type 2 diabetes mellitus (T2DM) patients with retinopathy. Methods: In this cross-sectional casecontrol study, 212 subjects enrolled which were categorized into 3 groups. Group-I included 30 subjects without diabetes, group-II consisted of 30 subjects with T2DM without retinopathy and group-III consisted of 152 subjects with T2DM and retinopathy. Serum IL-6 and IL-17 levels were determined by ELISA. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. Results: Longer mean duration of disease was detected in group-III than group-II (p=0.007). Highest IL-6 level was detected in group-II and highest IL-17 level was detected in group-I. For IL-6, significant differences were detected among groups in total, between Group-I and Group-III and between Group-II and Group-III (p<0.0001 each). Regarding IL-17, significant differences were found among groups in total (p=0.002) and between Group-I and Group-III (p=0.001). No significant difference in the percentages of HbA1c observed between groups. Conclusions: Age, gender and duration of diabetes contribute to T2DM retinopathy. Serum IL-6 and IL-17 were inversely associated with T2DM retinopathy.
Nadereh Naderi; Zahra Etaati; Mansoreh Rezvani Joibari; Seyed Alireza Sobhani; Said Hosseni Tashnizi
Volume 10, Issue 2 , June 2013, , Pages 118-126
Abstract
Background: Iron Deficiency Anemia (IDA) has been controversially linked to IL-4 production in previous studies. A predominant Th1 response leads to resistance against recurrent vulvovaginal candidiasis (RVVC), whereas a Th2 response exacerbates the disease. Objective: To investigate the possible effect ...
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Background: Iron Deficiency Anemia (IDA) has been controversially linked to IL-4 production in previous studies. A predominant Th1 response leads to resistance against recurrent vulvovaginal candidiasis (RVVC), whereas a Th2 response exacerbates the disease. Objective: To investigate the possible effect of iron deficiency on the host’s susceptibility to RVVC as a result of the Th1/Th2 cytokine polarization. Methods: We conducted a case-control study of 92 women in 4 groups based on strict inclusion and exclusion criteria: RVVC+IDA+ group consisted of 23 women with RVVC and IDA; RVVC+ IDA- group consisted of 23 women with RVVC without IDA; RVVC-IDA+ group consisted of 23 women without RVVC and with IDA and RVVC- IDA- group consisted of 23 healthy women. The iron parameters and key cytokines (IFN-γ, IL-10, IL-12, IL-4) were measured in blood samples. Results: Comparison of IL-4 production between RVVC+ IDA+ (12.2 ± 1.3 pg/ml) and RVVC+ IDA- (2.4 ± 4.0 pg/ml) groups (p=0.044), between RVVC- IDA+ (14.6 ± 1.7 pg/ml) and RVVC- IDA- (1.28 ± 3.6 pg/ml) groups (p=0.006), between RVVC- IDA+ (14.6 ± 1.7 pg/ml) and RVVC+ IDA-) 2.4 ± 4.0 pg/ml) groups (p=0.009) and also between RVVC+ IDA+ and RVVC- IDA- (1.28 ± 3.6 pg/ml) groups (p=0.03) showed significant differences. We found a significant positive correlation between IL-4 and total iron binding capacity (TIBC, p=0.046) and between serum IL-10 and Hb levels (p=0.041) in the RVVC+ IDA- group. There was also a significant negative correlation between serum IL-4 and levels of serum iron (SI, p=0.041) in the RVVC- IDA- group. Conclusion: It seems that IDA determines the balance between and the intensity of Th1 and Th2 arms of the immune response and leads to a deviation toward Th2 response which could contribute to recurrence of candidiasis.
Soghra Khazardoust; Pouya Javadian; Bahram Salmanian; Farnaz Zandevakil; Fatemeh Abbasalizadeh; Shohreh Alimohamadi; Sedigheh Borna; Tooba Ghazanfari; Sedigheh Hantoushzadeh
Volume 9, Issue 3 , September 2012, , Pages 199-207
Abstract
Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration ...
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Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration of women at risk of preterm labor. Methods: In a randomized clinical trial of 80 prime-gravid women in preterm labor between 34 and 37 weeks of gestation, cervical fluid was collected. Endocervical concentration of inflammatory cytokines were analyzed before and 48 hours after betamethasone treatment for the evaluation of IL-8, IL-17, IFN-γ and TGF-β. Wilcoxon and Mann-Whitney tests were employed for statistical analysis. χ2 and Student’s t tests were used whenever needed. Results: All the measured cytokines showed significant changes in the betamethasone treated group. IL-17 (p=0.001), IL-8 (p=0.001), and IFN- γ (p<0.05) decreased significantly, while TGF-β had a significant increase (p<0.05). In the patients who delivered before or on the 7th day of admission, IL-17, IL-8, and IFN-γ levels were all significantly higher. However, TGF-β decreased significantly in the same samples in the betamethasone treated group (p<0.05). Conclusion: Betamethasone significantly decreases the endocervical pro-inflammatory cytokine concentrations in patients with preterm labor.
Samira Rajaei; Amir Hassan Zamani; Mahmood Jeddi-Tehrani; Maryam Tavakoli; Afsaneh Mohammadzadeh; Ali Dabbagh; Mahroo Mirahmadian
Volume 8, Issue 4 , December 2011, , Pages 201-208
Abstract
Background: Repeated Implantation Failure (RIF) is one of the most intricate obstacles in assisted reproduction. The cytokine and chemokine composition of uterine cavity seem to play important roles in the implantation process. Objective: To compare the cytokine profile in the endometrium of normal fertile ...
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Background: Repeated Implantation Failure (RIF) is one of the most intricate obstacles in assisted reproduction. The cytokine and chemokine composition of uterine cavity seem to play important roles in the implantation process. Objective: To compare the cytokine profile in the endometrium of normal fertile women and those with repeated implantation failure. Methods: After enzymatic digestion of endometrial tissues, whole endometrial cells and endometrial stromal cells from RIF and normal fertile women were cultivated and stimulated for cytokine secretion. The levels of IL-10, TGF-β, IFN-γ, IL-6, IL-8 and IL-17 in culture supernatants of the two groups were assayed by ELISA and compared together. Results: Endometrial stromal cells and whole endometrial cells of normal fertile women produced higher levels of IL-6, IL-8 and TGF-β compared to RIF group, although this difference was statistically significant only in endometrial stromal cells (p=0.005, 0.002 and 0.001, respectively). In addition, endometrial stromal cells of normal fertile women produced lower levels of IL-10 in comparison with RIF group (p=0.005). Conclusion: Disturbances in cytokine production at the feto-maternal interface could be a cause of implantation failure. A pro-inflammatory cytokine milieu seems to be pivotal for successful implantation.
Mandana Sattari; Alireza Fathiyeh; Fatemeh Gholami; Hassan Darbandi Tamijani; Mahdi Ghatreh Samani
Volume 8, Issue 1 , March 2011, , Pages 20-26
Abstract
Background: Growth factors play a major part in wound healing in many tissues including the periodontium. Transforming growth factor-β1 (TGF-β1) is one of these factors present in the gingival crevicular fluid. In addition, it is considered as one of the most important anti-inflammatory cytokines. ...
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Background: Growth factors play a major part in wound healing in many tissues including the periodontium. Transforming growth factor-β1 (TGF-β1) is one of these factors present in the gingival crevicular fluid. In addition, it is considered as one of the most important anti-inflammatory cytokines. Interleukin-1β is a proinflammatory cytokine that presents itself in gingival inflammation and the GCF. Such factors might be of value as prognostic markers of wound healing activity and the therapeutic progress following flap surgery. Objective: The aim of this study was to evaluate the effect of surgical flap on the concentration of IL-1β and TGF-β in the GCF of patients with moderate to severe chronic periodontitis. Methods: The GCF samples were collected, using the Perio-Paper strip at phase 1 (pre-surgery), phase 2 (4th week post surgery) and phase 3 (12th week post surgery) from 20 sites of 10 patients undergoing flap surgery. After the elution, IL-1β and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean TGF-β and IL-1β concentration decreased from phase 1 to phase 3 (p<0.05). There were no significant statistical correlations between IL-1β and TGF-β1 concentrations in the 3 assessment phases. There was a significant statistical correlation between TGF-β1 concentrations and the Plaque Index (PI) in phase 2 (p<0.05). There was a significant statistical correlation (p<0.05) between IL-1β and TGF-β1 concentration and the probing pocket depth (PPD). Conclusion: The flap surgery has a significant effect on decreasing IL-1β concentration. In the case of TGF-β1, probably the decrease in the concentration after treatment might be due to the removal of the inflammatory stimulants.
Esra Kazak; Sergio Costa Oliveria; Güher Goral; Halis Akalin; Emel Yilmaz; Yasemin Heper; Haluk Barbaros Oral
Volume 7, Issue 3 , September 2010, , Pages 132-141
Abstract
Background: Because of high morbidity of the brucellosis in humans and the potential use of the microorganism as an agent of biologic warfare, protection of effective vaccines and specific diagnostic reagents become necessary to eradicate brucellosis. Objective: In this study we aimed to investigate ...
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Background: Because of high morbidity of the brucellosis in humans and the potential use of the microorganism as an agent of biologic warfare, protection of effective vaccines and specific diagnostic reagents become necessary to eradicate brucellosis. Objective: In this study we aimed to investigate the cytokine responses and changes in peripheral blood lymphocyte subgroups of acute brucellosis patients in response to L7/L12 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) recombinant proteins derived from Brucella abortus. Methods: levels of IFN-γ, IL-4 and IL-10 secreted from PBMCs of 25 acute brucellosis patients and 15 healthy controls, stimulated with Phytohemagglutinin (PHA), L7/L12 or GAPDH were measured by ELISA. Furthermore alterations in lymphocyte subgroups in response to these Brucella antigens were determined by flow cytometry. Results: Extracellular IFN-γ levels were found to be elevated after stimulation with L7/L12 in patients with acute brucellosis, whereas no significant changes were found in IL-4 and IL-10 levels. Similar data was also obtained with GAPDH, but the stimulation of IFN-γ production was not observed in all patients and was not as strong as that observed for L7/L12. Moreover, when the distribution of lymphocytes subgroups (CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+, CD3+CD69+ and CD3+CD152+) was evaluated, it was found that the stimulation with L7/L12 and GAPDH only led to an increase in the percentage of CD3+CD69+ lymphocytes. Conclusion: These data indicate that Brucella abortus L7/L12 or GAPDH induce a Th1 type immune response in acute brucellosis patients. Additionally, these recombinant proteins, especially L7/L12, may be used in new vaccine preparations and diagnostic tests.
Nader Tajik; Tohid Kazemi; Aliakbar Delbandi; Ahad Ghods; Alireza Salek Moghaddam
Volume 3, Issue 4 , December 2006, , Pages 150-156
Abstract
Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated ...
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Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated donor (LURD) kidney transplantation. Methods: A total of 42 renal transplants performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and followed up for 3 months post-transplantation were included. Using PCR-SSP, HLA-DR alleles (DR1- 18) of recipients and donors and gene polymorphisms in TNF-a, TGF-b1, IL-10, IL- 6, and IFN-g of recipients were determined. Results: Acute rejection was observed in 11(26.2%) of renal recipients. The frequency of one and two HLA-DR mismatches in rejector group was 2(18.2%) and 9(81.8%) and in non-rejector group was 13(41.9%) and 17(54.8%), respectively. HLA-DR incompatibility was not significantly higher in rejector (1.82 0.40) compared with non-rejector (1.52 0.57) recipients (P=0.069) and more than half of non-rejectors had completely mismatched HLA-DR antigens with donors. Polymorphisms associated with the mentioned cytokines had no correlation with acute rejection. Conclusion: The predictive value of HLA-DR mismatching for acute rejection is not as prominent in LURD kidney transplantation as in the cadaveric one. In addition, we failed to demonstrate an association between combined cytokine genotypes and HLA-DR matching with acute rejection. Further and more detailed immunogenetic investigations are required in order to have a better prediction of the transplant outcome.
