Roghayeh Rahimi; Ahmad Zavaran Hosseini; Fatemeh Yari
Volume 5, Issue 4 , December 2008, , Pages 207-211
Abstract
Background: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N. Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1 or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to in-hibit NK cell cytolysis. Thus, although the biological functions ...
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Background: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N. Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1 or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to in-hibit NK cell cytolysis. Thus, although the biological functions of HLA-G1 and HLA-G5 proteins are abrogated, other isoforms such as HLA-G2 can replace their roles. Stud-ies on the null allele of HLA-G gene could be useful in understanding the genetic vari-ants of HLA-G alleles in ethnic groups. Objective: The goal of this research was to de-termine the frequency of HLA-G*0105N null allele in Iranian healthy subjects. Meth-ods: The frequency of HLA-G*0105N null allele was evaluated in Iranian healthy sub-jects by PCR-RFLP method. Genomic DNA was isolated from the whole blood of 100 randomly selected, healthy, unrelated Iranian individuals using salting-out technique followed by PCR amplification of the exon 3 of HLA-G gene. PCR products were di-gested with PpUM-1 and the resulted fragments were analyzed using gel electrophore-sis. Results: In this study the restriction enzyme digestion confirmed homozygous HLA-G*0105N null allele for 9 % of the population. Furthermore obtained results indi-cated that the total frequency of HLA-G*0105N null allele was 20 % in the studied population of Iran. Conclusion: The final data analysis showed that the total frequency of this allele in Iranian people was higher than other ethnic groups that have been stud-ied so far.
Siamak Sandoghchian Shotorbani; Yue Zhang; Samuel Essien Baidoo; Huaxi Xu; Mohammad Ahmadi
Volume 8, Issue 4 , December 2011, , Pages 209-217
Abstract
Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In ...
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Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In this study, a chicken collagen-II-induced experimental arthritis (CIA) model was used in DBA/1 mice to investigate the relationship between IL-4 and IL-17 as well as other inflammatory factors. On the 38th day after the mice were induced with CIA, the expression of IL-17 and IL-4 as well as IFN-γ and IL-13 in sera of the mice was measured by QRT-PCR and ELISA. Result: The result of QRT-PCR analysis of IL-17 and IL-4 mRNA levels in the spleen showed that IL-17 is increased significantly at the onset of CIA in the spleen (p<0.01). Meanwhile, IL-17 is generally reduced at the peak of CIA but IL-4 is increased significantly at this peak in the spleen (p<0.05) when the weight of the animal was taken into consideration. Conclusion: IL-4 can be involved in the production of IL-17 at especially the peak of CIA. These results imply that the inhibition of IL-17 may decrease the expression of IL-1β and IL-6 production which will result in the aggravation of arthritis.
Mohammad Reza Akbari; Mojtaba Saadati; Hosein Honari; Hadi Mohammad Ghorbani
Abstract
Background: Shigella flexneri is a pathogen responsible for shigellosis around the world, especially in developing countries. Many immunogenic antigens have been introduced as candidate vaccines against Shigella, including N-terminal region of IpaD antigen (NIpaD). Objective: To evaluate the efficiency ...
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Background: Shigella flexneri is a pathogen responsible for shigellosis around the world, especially in developing countries. Many immunogenic antigens have been introduced as candidate vaccines against Shigella, including N-terminal region of IpaD antigen (NIpaD). Objective: To evaluate the efficiency of O-metylated free trimethyl chitosan nanoparticles (TMC NPs) in the oral delivery of NIpaD. Methods: TMC was synthesized by a two-step method from high molecular weight chitosan. The recombinant NIpaD protein was used as the immunogen. The protein was overexpressed in E. coli BL21 (DE3) and characterized by gel electrophoresis. The NIpaD-loaded TMC NPs were synthesized by ionic gelation method and were characterized by electron microscopy. NPs were orally administered to guinea pigs and specific humoral and mucosal immune responses were assessed by serum IgG and secretory IgA, respectively. The protectivity of the formulation was assessed by keratoconjunctivitis (Sereny) test. Results: The immunized guinea pigs showed a significant raise in rNIpaD-specific serum IgG and faecal IgA titers. Specific secretory IgA was detected in eye-washes. Sereny test results showed that immunized animals vaccinated with IpaD-loaded TMC NPS tolerated the wild type of Shigella flexneri 2a in Sereny test. However, in the group immunized with NIpaD antigen and non-immunized group, no increase was observed in antibody titer against NIpaD. These animals were infected following the challenge with Shigella flexneri 2a (p<0.0152). Conclusion: The recombinant rNIpaD formulated with TMC obtained from high molecular weight chitosan, can be considered as a mucosal vaccine against Shigella flexneri through oral route.
Ghasem Mosayebi; Shaban Ali Alizadeh; Ali Alasti; Alireza Amouzandeh Nobaveh; Ali Ghazavi; Mahsa Okhovat; Mohammad Rafiei
Volume 10, Issue 4 , December 2013, , Pages 216-228
Abstract
Background: The appendix is considered as part of the gut-associated lymphoid tissue; however, lymphocyte subsets in this tissue are not fully defined. Objective: To investigate and compare the function and phenotype of lymphocyte subsets in peripheral blood and appendix of patients with normal and inflamed ...
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Background: The appendix is considered as part of the gut-associated lymphoid tissue; however, lymphocyte subsets in this tissue are not fully defined. Objective: To investigate and compare the function and phenotype of lymphocyte subsets in peripheral blood and appendix of patients with normal and inflamed appendix tissues. Methods: Peripheral blood samples and appendiceal mononuclear cells were obtained from 81 patients (mean age; 23 ± 10.5 years), clinically suspected of having appendicitis. The phenotypic characteristics of lymphocyte subsets in peripheral blood (before and 48-72 hrs after appendectomy) and in appendix tissue were analyzed by three color-flow cytometry. The proliferative response of mononuclear cells was assessed by MTT method. Results: The frequency of CD19+DR+, HLA-DR+ and CD19+ cells in the appendix tissue were significantly higher than that of the peripheral blood in all the groups (p<0.001). The percentage of CD19+ cells and HLA-DR+CD19+ cells significantly decreased after appendectomy in the peripheral blood of the patients with acute appendicitis (p=0.047 and p=0.03, respectively). CD19 and HLA-DR plus CD19 had better diagnostic efficiency compared with T cell markers (area under the ROC curve [AUC]= 0.76 and 0.73, respectively). Conclusion: These results indicate a significant difference in CD19+ and HLA-DR+ lymphocytes between peripheral blood and the appendix tissue.
Mojgan Mohammadi; Philip J.R. Day
Volume 7, Issue 4 , December 2010, , Pages 217-225
Abstract
Background: The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor (VEGF) expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there ...
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Background: The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor (VEGF) expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there are many studies showing that some gene polymorphisms significantly influence the pharmacokinetics of immunosuppressive drugs. Objective: The aim of this study was to determine the influence of immunosuppressive drugs on VEGF production in individuals with different VEGF genotypes. Methods: ARMS-PCR was used to genotype VEGF polymorphisms at positions -1154 and -2578 within the promoter of VEGF gene. A VEGF-specific ELISA was used to determine the influence of immunosuppressive drugs on VEGF production in PBMCs of individuals with different VEGF genotypes. Results: Suppressive effect of mycophenolic acid was observed just in individuals with GG -1154/CC -2578, GG -1154/CA -2578 and GA -1154/CC -2578 haplotypes. Additionally, VEGF was significantly suppressed in all individuals after treatment with rapamycin except those who had AA -1154/CA -2578 and AA -1154/AA -2578 VEGF genotype combinations. Conclusion: Results of a recent study revealed that MMF treatment might be effective in preventing chronic renal rejection only in recipients with IL-10 high producer genotype. Additionally result of another study showed that CYP3A5 genotype markedly influences the pharmacokinetics of rapamycin in kidney transplant recipients. Therefore with regard to our results, different suppressive effect of mycophenolic acid and rapamycin on VEGF production might also be dependent on VEGF genotype.
Behrouz Gharesi-Fard; Leila Jafarzadeh; Jaleh Zolghadri; Hossein Haghbin
Volume 9, Issue 4 , December 2012, , Pages 234-240
Abstract
Background: Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. ...
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Background: Normal pregnancy is thought to be dependent on Th2 deviation, while Recurrent Pregnancy Loss (RPL) and Pre-eclampsia (PE) appear to be biased toward the Th1 immune response. It is believed that the soluble form of CD30 (sCD30) is an index of Th2 immune response or modulator of Th1/Th2 responses. Objective: The aim of this study was determination of the sCD30 level in RPL and PE patients. Methods: The sCD30 level was measured in sera of a group of normal non-pregnant women (N=43) and compared with normal pregnancy at the first (N=42) and third (N=42) trimester. Furthermore, the level of sCD30 in the normal first and third trimester pregnancies were compared with that of RPL (N=38) and severe pre-eclamptic (N=41) patients, respectively. sCD30 levels were measured by ELISA method and student t-test was used for statistical analysis. Results: The mean level of sCD30 at the first trimester in normal pregnancy was significantly elevated as compared with normal non-pregnant women (21.4 vs. 15.2 ng/ml, p<0.0001). A significant difference between sCD30 concentration at the first and third trimester of normal pregnancies was also observed (21.4 vs. 14.3 ng/ml, p<0.0001). Interestingly, the sCD30 concentration did not show any significant changes at the first trimester of normal pregnancy as compared with RPL (21.4 vs. 20.9 ng/ml) and third trimester of normal pregnancy as compared with PE (14.3 vs. 13.1 ng/ml). Conclusion: The data of this study indicated that the concentration of sCD30 in serum during pregnancy period is not associated with RPL or PE and serum sCD30 is not a good correlate of Th2 immune responses in pregnancy.
Mohammad Hossein Nikoo; Seyed Rahmatollah Taghavian; Hossein Golmoghaddam; Narges Arandi; Alireza Abdi Ardekani; Mehrnoosh Doroudchi
Volume 11, Issue 4 , December 2014, , Pages 246-258
Abstract
Background: Atrial Fibrillation (AF) is the most common cardiac arrhythmia and an independent risk factor for stroke among the elderly. A role for inflammation in the atrial remodeling as well as development and recurrence of AF is known. Objective: To compare IL-17A between patients with different types ...
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Background: Atrial Fibrillation (AF) is the most common cardiac arrhythmia and an independent risk factor for stroke among the elderly. A role for inflammation in the atrial remodeling as well as development and recurrence of AF is known. Objective: To compare IL-17A between patients with different types of AF and healthy individuals. Methods: IL-17A was measured in sera of 112 patients and 107 healthy age/sexmatched controls using ELISA assay. In sera of 26 patients with elevated IL-17A (>1 Pg/ml), CCL5 and CCL18 levels were also measured. Results: IL-17A was significantly increased in patients with AF compared to controls (1.28 ± 3.5 vs. 0.19 ± 0.64 Pg/ml, p=0.001). There was no significant difference in the level of IL-17A between different types of AF. IL-17A was significantly higher in patients with a history of coronary artery bypass graft compared to other patients (p=0.01). A significant positive correlation between IL-17A and CCL18 concentration was found (p=0.001). An increase in the Neutrophil/Lymphocyte ratio (NLR) was observed in patients with elevated serum IL-17A compared to other patients (p=0.006). Male patients showed higher increase in NLR (p=0.007) which was accompanied by a decrease in CCL5 (p=0.000) and a marginal increase in CCL18 (p=0.085) compared to females. There was an increase in CCL5 levels in patients receiving Acetylsalicylic Acid (ASA) therapy (p=0.046). Conclusions: The increase in IL-17A levels is related to the AF pathology mediated by neutrophils and monocytes. The current study signifies the role of immune cells and cytokines in the pathology of AF.
Mitra Rafiee; Marjan Gharagozloo; Ataollah Ghahiri; Ferdous Mehrabian; Mohammad R. Maracy; Shirin Kouhpayeh; Ina Laura Pieper; Abbas Rezaei
Volume 12, Issue 4 , December 2015, , Pages 252-262
Abstract
Background: Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1 a, 25-dihydroxy-vitamin-D3 (vitamin D3) may ...
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Background: Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1 a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. Objectives: To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. Methods: The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL- 17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. Results: Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p <0.05). Conclusion: Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.
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.
Alireza Tahamtan; Mohammad Barati; Alijan Tabarraei; Seyed Reza Mohebbi; Sadegh Shirian; Ali Gorji; Amir Ghaemi
Volume 14, Issue 4 , December 2017, , Pages 281-292
Abstract
Background: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated event. Objective: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the ...
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Background: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated event. Objective: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection. Methods: We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on an a master cycler ep realplex and the data were analyzed using an online data analysis software. Results: Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression. Conclusion: Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a roles in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.
Xiaoling Liu; Xiaojia Liu; Yu Ren; Hongxin Yang; Xiaolei Sun; Haiyun Huang
Abstract
Background: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). Objective: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. Methods: Out of 127 patients ...
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Background: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). Objective: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. Methods: Out of 127 patients with potential eligible AR, 60 were randomly assigned into two groups and were finally included in our analysis (n=30 for each intervention). The patients with potential eligible AR were randomly allocated to intervention with desloratadine citrate disodium (DCD, 8.8 mg/day) without and with vitamin D3 nasal drops (1.5х106 IU, once/week) for four weeks. Thirty healthy control subjects were included in our study. We assessed the changes in the serum 25(OH)D, peripheral blood eosinophils, interleukin (IL)-4 levels, and nasal symptoms. Serum 25(OH)D, peripheral blood eosinophils, and IL-4 levels were detected respectively with liquid chromatography-tandem mass spectrometry (LC-MS/MS), a blood detector, and enzyme-linked immunosorbent assay. Results: Our patients who received vitamin D3 adjuvant therapy had a higher serum 25(OH)D level (47.57 ± 2.83 vs. 31.51 ± 2.95 ng/ml, p=0.000) and lower AR symptoms score (2.07 ± 1.89 vs. 3.37 ± 1.50, p=0.005), serum IL-4 (10.38 ± 3.41 vs. 12.79 ± 5.40 pg/ml, p=0.043), and peripheral blood eosinophils (0.34 ± 0.09 vs. 0.41 ± 0.10 109/l, p=0.003) compared with DCD single treatment. The efficacy rates of DCD with and without vitamin D3 in AR were 97% and 84%, respectively. Conclusion: Nasal vitamin D3 combined with DCD could improve the clinical symptoms of AR. Vitamin D3 adjunct therapy showed significant effects on inhibiting inflammation in patients with AR. We concluded that vitamin D3 supplementation could be an effective adjuvant therapy in AR patients.
Somayeh Rezaeifard; Akbar Safaei; Abdolrasoul Talei; Zahra Faghih; Nasrollah Erfani
Abstract
Background: NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. Objective: To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as ...
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Background: NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. Objective: To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as activated T lymphocytes, in tumor draining lymph nodes (TDLNs) of patients with breast cancer (BC) and their association with different clinic-pathological features of the patients. Methods: Axillary lymph nodes were obtained from 30 Iranian women with breast cancer. After routine pathological evaluations, mononuclear cells were separated from their lymph nodes and incubated with appropriate fluorochrome conjugated monoclonal antibodies specific for CD3, HLA-DR, CD16/56, and Vα24Jα18-TCR. Data were collected on a four-color flow cytometer and analyzed by CellQuest software. Results: The mean percentages of NK (CD3-CD16/56+), NKT (CD3+CD16/56+) and iNKT (Vα24Jα18-TCR+) cells in TDLNs mononuclear cells of BC patients were 2.04%, 2.44% and 0.1%, respectively. A significant decrease in the percentages of NK and iNKT subsets in patients with grade I was observed compared to grade III (p=0.03 and p=0.01, respectively). Moreover, NK cells were increased in patients with grade III of BC compared to grade II (p= 0.003). Conclusion: The increase in the percentage of NK and iNKT cells in TDLNs of patients with higher grade of BC might suggest a suppressive phenotype for these cells in breast cancer, which merit more functional investigation.
Maryam Asadi; Razie Kiani; Vahid Razban; Seyed Nooreddin Faraji; Amirhossein Ahmadi; Jafar Fallahi; Amin Ramezani; Nasrollah Erfani
Abstract
Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.Objective: We have designed and generated an ...
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Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies.Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated.Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner.Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.
Abdol Rahim Nikzamir; Taghi Golmohammadi; Manouchehr Nakhjavani; Mahine Zahraei; Ali Akbar Amirzargar
Volume 3, Issue 1 , March 2006, , Pages 23-29
Abstract
Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes ...
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Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy.
Masooma Abdullahi; Reza Ranjbaran; Soheaila Alyasin; Zeinab Keshavarz; Amin Ramezani; Abbas Behzad-Behbahani; Sedigheh Sharifzadeh
Volume 13, Issue 1 , March 2016, , Pages 27-36
Abstract
Background: Asthma is very common in children and its diagnosis is based on clinical manifestations, which can be misdiagnosed as other respiratory diseases with similar signs and symptoms. Objective: To analyze the expression of ST2L and CD203c in the diagnosis of pediatric asthma. Methods: Basophils ...
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Background: Asthma is very common in children and its diagnosis is based on clinical manifestations, which can be misdiagnosed as other respiratory diseases with similar signs and symptoms. Objective: To analyze the expression of ST2L and CD203c in the diagnosis of pediatric asthma. Methods: Basophils were purified from whole blood samples of patients and healthy controls using Ficol-Paque gradient and Basophil Isolation Kit. RNA extraction was done by RNX-Plus solution and after synthesis of cDNA, the gene expression was analyzed by means of real time PCR. Results: Patients expressed significantly higher levels of CD203c than healthy controls (p=0.01). Although there was an increase in the transcription level of ST2L gene in patients, the results were not statistically significant compared to those obtained from the healthy controls (p>0.05). A Specificity of 60% and a sensitivity of 73% were foundusing ROC curve for CD203c expression. Patients with positive family history of asthma exhibited more CD203c and ST2L expression (p<0.05). Conclusion: It is proposed that determining CD203c expression by real time PCR may be an effective technique for diagnosis of pediatric asthma.
Mohammad Jafar Mahmoudi; Maryam Mahmoudi; Fereydoon Siassi; Fazel Shokri; Mohammad Reza Eshraghian; Amir Hassan Zamani; Reza Chahardoli; Mona Hedayat; Jalal Khoshnoodi; Hashem Nayeri; Nima Rezaei; Ali-Akbar Saboor-Yaraghi
Volume 8, Issue 1 , March 2011, , Pages 27-33
Abstract
Background: Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis. Objective: ...
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Background: Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis. Objective: The purpose of this study was to investigate the degree of peripheral blood mononuclear cells (PBMC) vulnerability to in vitro oxLDL-induced cytotoxicity from atherosclerotic patients in comparison to healthy individuals. Methods: Thirty patients with atherosclerotic lesions, confirmed by angiography, and 30 matched healthy individuals were investigated. PBMC was prepared from individuals' blood samples which were further stimulated with low dose (1 μg/mL) and high dose (50 μg/mL) of extensively oxidized LDL. MTT assay was utilized to measure cell viability and proliferation. Stimulation index (SI) was calculated as mean ratio of optical density (OD) of the stimulated cells divided by OD of untreated cells. Results: Low dose oxLDL treatment caused no significant proliferative or cytotoxic effect in the control group; however, similar treatment caused significant cytotoxic effect in the patient group compared to the controls (p=0.026). High dose oxLDL treatment induced more significant cytotoxicity in the patient compared to the control group (p=0.006). Comparison of the SI between the two groups of patients and controls showed significantly lower index by either the low (p=0.03) or the high dose (p<0.001) oxLDL in the patients compared to the controls. Conclusions: PBMC from patients with atherosclerosis showed increased susceptibility to oxLDL-induced cytotoxicity. Our results imply that prolonged exposure to elevated levels of circulating oxLDL could weaken the cellular defense mechanisms by progressive depletion of the pool of antiapoptotic proteins, rendering the cells more vulnerable to oxLDL-induced cell death.
Hamid Reza Jahadi Hosseini; Eskanadar Kamali Sarvestani; Mitra Akbari; Mahnaz Mosallaei
Volume 6, Issue 1 , March 2009, , Pages 28-32
Abstract
Background: Human cornea expresses functional Fas-ligand capable of killing Fas+ activated lymphocytes. Fas expression is partly regulated by -670 A/G polymorphism in the promoter region of Fas gene. Objective: The aim of the present study is to determine the association between Fas-670A/G polymorphism ...
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Background: Human cornea expresses functional Fas-ligand capable of killing Fas+ activated lymphocytes. Fas expression is partly regulated by -670 A/G polymorphism in the promoter region of Fas gene. Objective: The aim of the present study is to determine the association between Fas-670A/G polymorphism and survival of corneal transplantation. Methods: In 276 graft recipients who mainly underwent penetrating keratoplasty because of keratoconus, bullous keratopathy and corneal opacity, Fas -670 A/G polymorphism was determined by allele specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques. Results: There was no statistically significant relationship between Fas -670 A/G polymorphism and rejection episode (p=0.35). Moreover, the relationship between this polymorphism and rejection episode outcome (transplant recovery vs failure) was not statistically significant (p=0.13). Conclusion: The results of the present study show no significant correlation between corneal graft rejection, rejection recovery and Fas -670A/G gene polymorphism.
Afsoon Afshari; Ramin Yaghobi; Mohammad Hossein Karimi; Mojtaba Darbooie; Negar Azarpira
Volume 11, Issue 1 , March 2014, , Pages 29-39
Abstract
Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute ...
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Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute rejection. Methods: Ninety seven adult liver transplant patients who enrolled in this cross sectional study were divided into Non- Acute Rejected (Non-AR) and Acute Rejected (AR) patient groups. Three blood samples were collected from each patient in days 1, 4 and 7 post liver transplantation. The IL-17 mRNA levels were evaluated using an in-house real time PCR protocol. IL- 17 protein levels were also analyzed in Non-AR, AR and also control groups using ELISA method. Results: The IL-17 mRNA expression level continuously increased in AR patients in all days of follow-up post liver transplantation. IL-17 expression was, however, down regulated after day 4 post-transplant follow-up in Non-AR patients. Both IL-17 mRNA expression and protein levels were also significantly increased in AR patients compared with Non-AR ones. Conclusion: Based on these findings, significant increase of IL-17 mRNA and protein levels in AR patients highlights the important role of IL-17 in acute liver rejection.
Hasan Ebrahimi; Masoud Soleimani; Mohammad Kazemi Arabadadi; Naser Ajmadbeigi; Gholamhossein Hassanshahi; Akbar Farjadfar; Derek Kennedy
Volume 7, Issue 1 , March 2010, , Pages 30-38
Abstract
Background: Unrestricted somatic stem cells (USSC) are cord blood stem cells that have been considered as candidates for the regulation of immune responses. Therefore, potential exists for their use in the suppression of immune response after transplantation surgery. Objective: The aim of this study ...
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Background: Unrestricted somatic stem cells (USSC) are cord blood stem cells that have been considered as candidates for the regulation of immune responses. Therefore, potential exists for their use in the suppression of immune response after transplantation surgery. Objective: The aim of this study was evaluation of the effect of USSC on mixed lymphocyte reaction (MLR) as a model for graft rejection. Methods: USSC and mesanchymal stem cells (MSC) were isolated and cultured from cord blood and bone morrow, respectively. The immunophenotypes of USSC and MSC were evaluated by flow cytometery and USSC and MSC were co-cultured with peripheral blood lympho-cytes (PBL) in an MLR to evaluate the immunomodulatory effect of these cells as a percentage of the control response. Results: Current study demonstrated that prolifera-tion of lymphocytes in the MLR was decreased after treatment with USSC, in a similar fashion to that seen with MSC. Conclusion: It can be concluded that USSC have simi-lar regulatory effects as MSC on the MLR, which can be used as an indicator for poten-tial organ rejection after transplantation. Therefore, the immunregulatory effect of these cells could be used in the clinic during organ transplantation and in the management of autoimmunity.
Shirin Farjadian; Shahrzad Rahimifar; Nasrollah Erfani; Ramin Lotfi
Volume 10, Issue 1 , March 2013, , Pages 31-39
Abstract
Background: A possible mechanism by which hyperthermia enhances tumor immunogenicity is the induction of NKG2D ligands on tumor cells. Although the expression of MHC class I chain-related protein A and B (MICA/B) has previously been reported in different carcinomas, there is no information about MICA/B ...
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Background: A possible mechanism by which hyperthermia enhances tumor immunogenicity is the induction of NKG2D ligands on tumor cells. Although the expression of MHC class I chain-related protein A and B (MICA/B) has previously been reported in different carcinomas, there is no information about MICA/B expression in liposarcomas. Objective: To investigate MICA/B induction in a human liposarcoma cell line (SW-872) after thermotherapy. Methods: SW-872 and HeLa cell lines were subjected to thermal stress for 1 h at 42, 44 and 46C, and after 2, 4 and 6 h of incubation at 37C, MICA/B expression was assessed at the mRNA and protein levels. Results: Despite high levels of MICA/B transcripts in SW-872 cells at baseline, the expression of these genes decreased significantly at both the mRNA and protein levels after almost all thermal treatments. Conclusion: Our data conclude that thermotherapy under 42-46°C had no effect on MICA/B induction on SW-872 liposarcoma cell line but the effects of fever-range temperatures remain to be tested on this cell line.
Hedieh Matloubi; Mohammad Vodjgani; Abbass Ali Nasehi; Mohammad Hossein Niknam; Anoushirvan Kazemnejad; Eisa Salehi; Tahereh Aboufazeli; Zahra Gheflati
Volume 4, Issue 1 , March 2007, , Pages 32-37
Abstract
Background: Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In re-cent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. ...
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Background: Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In re-cent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. Objective: To investigate the T cell response to phytohaemagglutinin (PHA) and determine the serum levels of anti-nuclear antibody (ANA), anti-cytoplasmic antibody (ACA), and circulating immune complexes (CIC) in schizophrenic patients. Methods: A total of 30 drug-free schizophrenic patients and 42 healthy controls were enrolled in this study. T cell proliferation in response to PHA was measured using Methyl Thiazol Tetrazolium test. ANA and ACA were measured by indi-rect immunofluorescence. CIC concentration was determined using poly ethylene glycol precipitation assay. Results: Mean PHA response was 1.96 ± 0.83 in patients and 3.72±1.39 in healthy controls (p < 0.001). ANA and CIC concentrations were not signifi-cantly different between two groups. In addition, ACA was detected only in patients. Conclusion: Increased production of ACA together with lower T cell response to mito-gens in our patients provides evidence for the involvement of autoimmune mechanisms in the pathogenesis of schizophrenia.
Marziyeh Mohammadi-Kordkhayli; Rayhane Ahangar-Parvin; Sayed Vahab Azizi; Maryam Nemati; Ali Shamsizadeh; Mohammad Khaksari; Sayed Mohammad Moazzeni; Abdollah Jafarzadeh
Volume 12, Issue 1 , March 2015, , Pages 35-49
Abstract
Background: It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. Objective: To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in C57BL/6 mice by immunization ...
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Background: It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. Objective: To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein mixed with complete Freund's adjuvant. The mice were administered with PBS or olive oil, intraperitoneally, in the control groups and vitamin D (200 ng every two days) in the treatment group, from day +3 to +30. At day 31, the mice were scarified and their spinal cords and brains were harvested. The expression of the IL-27 and IL-33 mRNA in the spinal cord was measured using real time-PCR. Results: In PBS- or olive oil-treated EAE mice the expression of IL-27 P28 mRNA was significantly lower than that in the healthy control group (p<0.002). In both PBS- and olive o il-treated EAE groups, the expression of IL-27 EBI3 mRNA was also lower than that observed in the healthy group, but the differences were not significant. In vitamin D-treated EAE group, the expression of IL-27 P28 and IL-27 EBI3 were significantly higher compared with the olive oil-treated EAE groups (p<0.002 and p<0.04, respectively). The expression of IL-33 was significantly higher in PBS-or olive oil-treated EAE groups compared with healthy mice (p<0.05 and p<0.02, respectively). Vitamin D significantly decreased the expression of IL-33 compared with PBSor olive oil-treated EAE mice (p<0.04, p<0.02, respectively). The PBS- or oliv -treated e oil EAE mice showed the clinical symptoms of EAE at days 9 and 10, respectively. The vitamin D-treated EAE group exhibited the symptoms at day 12 post immunization. The maximum mean clinical score and mean pathological scores were also significantly lower in vitamin Dtreated EAE group, in comparison with PBS- or olive oil treated EAE mice (p<0.001). Conclusion: Vitamin D may modulate the expression of IL-27 and IL-33 in the spinal cord of EAE mice and also ameliorate the clinical symptoms of the disease.
Naceur Mejri; Imed Eddine Hassen; Jenny Knapp; Mouldi Saidi
Volume 14, Issue 1 , March 2017, , Pages 35-50
Abstract
Background: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach. Objective: ...
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Background: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach. Objective: To elucidate immunosuppressive effects of bioactive factors contained in chromatographic fractions from hydatid cystic fluid (HCF) of Echinococcus granulosus. Methods: Hydatid cystic fluid was fractionated by reverse phase chromatography. Non-specific Concanavalin A-driven proliferation of spleen cells was used to determine specific inhibitory fractions. Trypan blue exclusion test and flowcytometry analysis were performed to check whether highly inhibitory fractions of HCF have apoptotic effect on peritoneal macrophages. Western blot analysis was used to determine proteolytic effects of parasitic antigens on major histocompatibility complex (MHC) class II (I-a) contained in membrane proteins extract from macrophages. Results: High concentrations of HCF and few of chromatographic fractions suppressed spleen cells proliferation. Fractions 7 and 35 were the highest inhibitory fractions. Specifically fraction 35 and to a lesser extent HCF induced apoptosis in peritoneal naive macrophages. However, HCF and the fraction 7 proteolytically altered the expression of MHC class II molecules on peritoneal macrophages. The proteolytic molecule was identified to be a serine protease. Macrophages taken at the chronic and end phase from cystic echinococcosis-infected mice were able to uptake and process C-Ovalbumine-FITC. These cells expressed a drastically reduced level of (I-a) molecules. Conclusion: Our study present new aspects of immune suppression function of E. granulosus. Further molecular characterization of apoptotic and proteolytic factors might be useful to develop immunotherapeutic procedure to break down their inhibitory effects.
Mohammad Taghi Goodarzi; Safyieh Ghahramany; Mohammad Hossien Mirmomeni
Volume 2, Issue 1 , March 2005, , Pages 36-42
Abstract
Background: Glycation of proteins is a non-enzymatic spontaneous process that occurs in diabetes mellitus and aging, altering the structure and function of proteins. IgG undergoes glycation leading to changes in its reactivity to antigen and fixation of complement. Objective: This study aimed ...
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Background: Glycation of proteins is a non-enzymatic spontaneous process that occurs in diabetes mellitus and aging, altering the structure and function of proteins. IgG undergoes glycation leading to changes in its reactivity to antigen and fixation of complement. Objective: This study aimed at revealing the effect of glycation on the interaction of IgG with anti-IgG using electroimmunoassay. Methods: Purified human IgG was glycated with different concentrations of glucose and different periods of treatment. Glycation was measured using thiobarbituric acid reaction. Glycated and non-glycated IgG were subjected to electroimmunoassay, and the height of the precipitated rings were measured and compared. Results: The results showed that IgG was glycated in vitro and the level of glycation was dependent on the glucose concentration and duration of treatment with glucose. The height of glycated IgG peaks formed in the electroimmunoassay was significantly lower than those of nonglycated IgG ( p < 0.01). Conclusion: The results indicated that in vitro glycation of IgG leads to structural changes altering its mobility in the electroimmunoassay. Moreover, it suggests that this alteration may cause the weakness of its interaction with anti-IgG. This phenomenon may play a role in the susceptibility of diabetic patients to infection.
