Masutaka Furue; Dugarmaa Ulzii; Yen Vu; Gaku Tsuji; Makiko Kido-Nakahara; Takeshi Nakahara
Abstract
Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles ...
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Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles in atopic inflammation. The expression of IL-4 and IL-13 as well as type 2 chemokines such as CCL17, CCL22 and CCL26 is increased in the lesional skin of AD. In addition, IL-4 and IL-13 down-regulate the expression of filaggrin in keratinocytes and exacerbate epidermal barrier dysfunction. Keratinocytes in barrier-disrupted epidermis produce large amounts of thymic stromal lymphopoietin, IL-25 and IL-33, conducing to type 2 immune deviation via OX40L/OX40 signaling. IL-31, produced by type 2 T cells, is a cardinal pruritogenic cytokine. IL-4 and IL-13 also amplify the IL-31-mediated sensory nerve signal. These molecules are particularly important targets for future drug development for AD.
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.
Ahmad Khalili; Zuhair Muhammad Hassan; Shahram Shahabi; Ali Akbar Pourfathollah; Seyed Nasser Ostad; Shokoofe Noori; Mehdi Mahdavi; Habib Haybar; Ladan Langroudi
Volume 10, Issue 2 , June 2013, , Pages 70-82
Abstract
Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, ...
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Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. Objectives: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Methods: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. Results: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. Conclusion: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
Shokoofe Noori; Zuhair Mohammad Hassan; Omid Salehian
Volume 10, Issue 1 , March 2013, , Pages 10-21
Abstract
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on ...
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Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects on reducing the tumor volume and shifting the cytokine profile were investigated. We also assessed if intraperitoneally injected Sclareol could improve the outcome of cancer therapy through suppressing the regulatory T cells. Results: The results confirmed a significant decrease in the tumor size. Furthermore, a significant decrease in the level of IL-4 and an increase in the level of IFN-γ were noticed in the intraperitoneally injected Sclareol group (p<0.05). It was also observed that the splenocytes of treated animals significantly increase in cell proliferation assay. Moreover, measurements of splenic T regulatory cell indicated that intraperitoneally injected Sclareol significantly decreased the number of splenic T regulatory cell. Conclusion: Our results suggest that Sclareol, by reducing T-reg cells frequency and also tumor size can enhance the effect of cancer therapy as an immunostimulant.
Mohammad Ali Ghayumi; Zahra Mojtahedi; Mohammad Javad Fattahi
Volume 8, Issue 4 , December 2011, , Pages 195-200
Abstract
Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) ...
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Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analysed using enzymelinked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.
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.
Maryam Robati; Ardeshir Ranjbari; Mehri Ghafourian Boroujerdnia; Zahra Chinipardaz
Volume 8, Issue 3 , September 2011, , Pages 170-175
Abstract
Background: Periodontitis is a multifactorial chronic inflammatory disease characterized by destruction of tooth-supporting tissues. Environmental and genetic factors as well as the immune system participate in this process. Recent studies have attempted to elucidate the role of cytokine networks involved ...
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Background: Periodontitis is a multifactorial chronic inflammatory disease characterized by destruction of tooth-supporting tissues. Environmental and genetic factors as well as the immune system participate in this process. Recent studies have attempted to elucidate the role of cytokine networks involved in periodontal diseases. Objective: To assess and compare the levels of IL-4, IL-6 and IL-12 in serum samples of patients with generalized aggressive periodontitis (GAgP) and control individuals. Methods: A total of 50 subjects were included in the study of which 25 patients had generalized aggressive periodontitis and 25 were healthy unrelated age and gender matched patients undergoing extraction and surgical crown lengthening (control group). Local blood samples of patients were collected from surgical sites of pocket reduction and from healthy individuals before tooth extraction or crown lengthening from non inflamed sites. The levels of IL-4, IL-6 and IL-12 were determined by an ELISA assay using serum samples separated from the whole blood of both groups. Results: The level of IL-4 increased significantly in control group in comparison with the test group (p=0.002). The amount of IL-6 in GAgP patients increased strongly compared with control group (p<0.0001). There was no significant difference between the two groups concerning the level of IL-12. Conclusion: There is an association between generalized aggressive periodontitis and low level of IL-4 as an anti-inflammatory cytokine, and high level of IL-6 as a proinflammatory cytokine. No correlation between IL-12 and generalized aggressive peridontitis was found.
Shokoofe Noori; Mohammad Taghikhani; Zuhair M. Hassan; Abdolamir Allameh; Ali Mostafaei
Volume 6, Issue 4 , December 2009, , Pages 216-224
Abstract
Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this ...
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Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this study, the immunotherapeutic effec-tiveness of Tehranolide was investigated by direct intra-tumoral injection. Methods: Tehranolide was purified from Artemisia diffusa, and its effect on the tumor volume was investigated. The splenocyte proliferation, shifting of cytokine profile, and the presence of naturally-occurring CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune response. Results: Analysis of immune response showed that, intra-tumoral injection of Tehranolide decreased the rate of tumor growth compared to control group. Furthermore, the proliferative response of mice treated with Tehranolide was en-hanced. In comparison with the control group, production of both IL-4 and IFN-γ was in-duced (p<0.05). The results indicated a decrease in tumor CD4+CD25+Foxp3+ T lym-phocytes in the Tehranolide-treated group compared to the control group. Conclusion: Treatment of tumors with Tehranolide attenuated CD4+CD25+Foxp3+ Treg cell-mediated immune suppression and elicited a persistent anti-tumor immunity against can-cer.
Mojgan Mohammadi; Mohammad Reza Bazrafshani; Philip.J Day; William. E.R. Ollier
Volume 6, Issue 3 , September 2009, , Pages 119-129
Abstract
Background: Vascular endothelial growth factor (VEGF) has a key role in angiogene-sis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region. Objectives: In this study, the association between the combination of VEGF –1154 G and –2578 ...
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Background: Vascular endothelial growth factor (VEGF) has a key role in angiogene-sis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region. Objectives: In this study, the association between the combination of VEGF –1154 G and –2578 C alleles and VEGF production by LPS-stimulated PBMCs was investigated. In addition; the relationship between VEGF poly-morphisms and the influence of TNF-α and IL-4 on VEGF production was studied. Methods: VEGF –1154 G/A and –2578 C/A were detected using ARMS-PCR. To de-termine the impact of combinations of these two polymorphisms on VEGF production; PBMCs were stimulated by LPS and VEGF production was measured by ELISA. Re-sults: The combinations of –1154 GG/-2578 CC and –1154 GG/-2578 CA were signifi-cantly associated with higher VEGF production (p<0.0001). Production of VEGF was significantly influenced by TNF-α in individuals who had certain VEGF genotype com-binations. Although VEGF production was dramatically suppressed by IL-4, it was not dependent on VEGF genotype. Conclusions: Since TNF-α has influence on the graft outcome, to avoid allocation of grafts from high TNF-α producer donors to recipients, it might be useful to predict and minimize graft rejection by having prior knowledge of TNF-α and also VEGF genotypes especially -1154 G/A and -2578 C/A VEGF.