New Approaches in Immunotherapy of Behçet Disease

Behçet Disease (BD) is an autoimmune disorder with recurrent ocular, vascular, central nervous system, articular, mucocutaneous, and gastrointestinal manifestations with unclear etiology and pathogenesis. The further characterization of inflammatory features of Behçet’s disease may eventually lead to development of better treatment options. Clinical and laboratory observations suggested an important role of IL-17, IL-21 and neutrophil-mediated process in the pathogenesis of BD. New therapeutic modalities target specific and nonspecific suppression of the immune system. The various non-specific immunosuppressive drugs, used either alone or in combinations, frequently fail to control inflammation or maintain remissions. Due to encouraging clinical results (i.e. Antigenic specification, prolonged survival with acceptable levels of toxicity); antibody-based drugs could be effective for the clinical management of Behçet’s disease

Interleukin-13 as an important cytokine: A review on its roles in some human diseases

Interleukin-13 (IL-13) as a pleiotropic cytokine acts through the IL-13Ra1/IL-4Ra complex to induce activation responses which contribute to the inflammatory diseases. Genetic polymorphisms in IL-13 and its receptor components have been proved to be associated with higher disease prevalence rates. Animal models such as in IL-13 deficient mice and transgenic animals also have been confirmed the critical role of this cytokine in the immune responses, mostly by IL-13 neutralization and IL-13/IL-4 dual neutralization strategies. This review highlights IL-13 structure as well as its pivotal roles in the normal physiologic and pathologic states. It is followed by a section on the recent findings on IL-13 receptors and signalling mechanisms to briefly summarize its functions in the immune systems. IL-13 roles in the human diseases such as asthma, systematic sclerosis, and some inflammatory diseases are described concisely. Finally some of the ongoing therapeutic applications are presented to comprehensively review IL-13 mediator roles

Analysis of Methylation and Expression Profile of Foxp3 Gene in Patients with Behçet’s Syndrome

Forkhead box P3 (Foxp3) gene is an important means in the Treg cells function, in both maintenances of immune tolerance and regulation of response. Epigenetic modifications of the foxp3 gene at its regulatory regions control the chromatin accessibility for the transcription factors and other transcriptional regulators in order to control Foxp3 expression. In addition, the methylation status of CpG islands within the Foxp3 promoter and regulatory elements regulate the expression of Foxp3. This study was performed to assess the role of the foxp3 gene in patients with Behçet’s syndrome (BS). Venous blood samples were collected from all participants and peripheral blood mononuclear cells (PBMC) were extracted through Ficoll-Hypaque method. Genomic DNA was randomly sheared by sonication and immunoprecipitated with a monoclonal antibody. The status methylation of the foxp3 gene was estimated in 108 blood samples of active BS patients and healthy individuals (controls); using methylation DNA immunoprecipitation (MeDIP) technique. Expression analysis was carried out; using Real-time PCR. The expression of foxp3 gene in the patients' group (mean±SD: 1.79±1.12) was significantly lower than the healthy group (mean±SD: 2.73±1.33) (p<001). Also, the methylation levels of Foxp3 promoter showed that its level in patients (mean±SD: 2.3±1.16) was higher than the healthy group (mean±SD: 1.85±0.59). However, this increase was not statistically significant (p>0.05). Also, these results indicated that increasing the amount of methylation of the foxp3 gene by reducing its expression leads to an increase and intensifying of the disease. The decrease in Foxp3 expression is possibly associated with hypermethylation of the gene, and it can be considered as a risk factor for BS. Future studies may be needed to identify the capability of specific DNA methylation alterations in this syndrome

The Study of HLA-G Gene and Protein Expression in Patients withRecurrent Miscarriage

Purpose: Although it has been frequently confirmed that HLA-G plays an important role in thereproduction and pregnancy, the pattern of HLA-G gene and its protein expression are rarelyaddressed in studies. Therefore we conducted this study in regard to evaluate the HLA-G geneand its protein expression in the women’s placenta with recurrent miscarriage.Methods: Placental samples were obtained from the women who were admitted for deliveryor abortion in Al Zahra and Taleghani hospitals, Tabriz, Iran. HLA-G gene expression wasdetermined by real-time polymerase chain reaction (PCR) and HLA-G protein expression wasassessed by western blotting and immunofluorescence staining in the tissue samples.Results: The results showed a significant decrease in the expression of gene and proteins ofHLA-G in the women with recurrent miscarriage compared to the control placental tissues.Conclusion: According to the obtained results, it was concluded that the decrement of HLA-Ggene and protein expressions are associated with recurrent miscarriage. Since there areconflicting results from other studies, it is suggested to conduct a more comprehensive similarstudy with greater sample size

The Effects of One-Stage Full-Mouth Disinfection and Qua-drant-Wise Scaling and Root Planing on Serum Levels of IL-17 and IL-1β and Clinical Parameters (A randomized Controlled Trial Study)

Objective: One-stage full-mouth disinfection technique (FMD) has been introduced to avoid cross-contamination between the treated and untreated regions between treatment sessions. Considering the role of inflammatory mediators in periodontitis, the aim of the present study was to compare the effects of FMD with the quadrant-wise scaling and root planing (Q-SRP) on serum levels of IL-17 and IL-1β in patients with moderate-to-severe chronic periodontitis.Materials and Methods: Twenty patients with chronic periodontitis were selected randomly and based on inclusion criteria in each group. In order to evaluate the periodontal status, the clinical parameters of bleeding on probing (BOP), clinical attachment level (CAL), probing depth (PD) and modified gingival index (MGI) were measured and recorded before treatment and at 2- and 4-month intervals after treatment. Immunologic parameters of the study such as IL-17 and IL-1β serum levels were determined by special laboratory kits at the same intervals. Data were analyzed by SPSS 15 statistical software. Statistical significance was defined at p<0.05.Results: The results showed a decrease in the means of IL-17 and IL-1β serum levels in both treatment modalities, with no statistically significant differences between the two study groups at the two time intervals (p>0.05). In the evaluation of periodontal parameters, all parameters exhibited clinical improvements in both groups, with no statistically significant differences between the two study groups (p>0.05).Conclusion: Based on the results of the present study it was concluded that both FMD and Q-SRP techniques result in improvements in periodontal indexes and decreases in the serum levels of IL-17 and IL-1β inflammatory mediators

Evaluation of interleukin 17: A polymorphism in patients with visceralleishmaniasis

Introduction: Visceral leishmaniasis (VL) is an infectious disease that it has spread in more than 60 countries, in Iran it is caused by Leishmania infantum. The infection is transmitted bysand flies, often affects children under 10 years of age, and it can be fatal if no treatment isundertaken. The progression of leishmaniasis infection in the host depends on cellularimmunity. Studies have associated immune responses against leishmaniasis to host genotype,resistance due to Th1 and T CD8+ cells, and responses leading to macrophage activation andparasite killing. The parasite can stimulate the production of interleukin 17A (IL-17A) byTh17. It was shown that IL-17A is strongly and independently associated with protectionagainst VL. Moreover, it seems that IL-17A has a complementary role in human protectionagainst VL. Methods: Blood samples were collected from 259 people among whom 88 were patients withhistory and clinical symptoms of leishmaniasis and 171 were healthy controls with no signs of infection. All participants were residents in an endemic area of VL in east Azerbaijanprovince, Iran. DNA extraction was performed using salting out method. Then, the controlgroup was divided into two groups of seropositive and seronegative by IFA (indirectfluorescent antibody) test, and for detecting polymorphism of IL-17A (197A\G) ARMS-PCR(Amplification refractory mutation system-Polymerase chain reaction) was used. Results: The result showed that the G allele was more frequent than the A allele among thegroups, but this difference was not statistically significant (P = 0.8). In addition, the GG genotype was more frequent than genotype A/G and A/A among the groups, but thisdifference was not statistically significant (P = 0.7). Conclusion: On the basis of the results, there was no significant association between VL andpolymorphism of IL-17A (197A\G

Echinophora platyloba DC (Apiaceae) crude extract induces apoptosis in human prostate adenocarcinoma cells (PC 3)

Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line. Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA) was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and DNA fragmentation gel electrophoresis. Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml). Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis. Conclusions: In summary, the E. platyloba extract attenuated the human prostate adenocarcinoma cell proliferation in vitro possibly by inducing apoptosis. E. platyloba is likely to be valuable for the treatment of human prostate adenocarcinoma

Effect of Non-surgical Periodontal Therapy on Serum and Salivary Concentrations of Visfatin in Patients with Chronic Periodontitis

Background and aims. Visfatin, mainly secreted by visceral adipose tissue, especially by macrophages, plays an impor-tant role in regulating the defense and immune functions, and functions as a growth factor, a cytokine, an enzyme and more importantly as a proinflammatory mediator. The aim of the present study was to evaluate the effect of non-surgical perio-dontal treatment on serum and salivary levels of visfatin in patients with generalized moderate-to-severe chronic periodonti-tis. Materials and methods. Eighteen patients with generalized moderate-to-severe chronic periodontitis were selected based on periodontal parameters of gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL) and radio-graphic parameters. Serum and salivary samples were collected at baseline and one month following non-surgical periodon-tal therapy (scaling and root planing ([SRP]). Visfatin levels were measured using an ELISA kit. Data were analyzed by SPSS 15, using paired t-test and Pearson’s correlation coefficient. Results. Mean salivary and serum levels of visfatin significantly decreased after non-surgical periodontal treatment (P<0.05). Changes in salivary visfatin levels were more prominent. Conclusion. According to the findings of this study it seems that there is a direct relationship between periodontal tissue inflammation and disease activity with salivary and serum visfatin levels

Increased IL-17A but decreased IL-27 serum levels in patients with Multiple Sclerosis

Background: Effector CD4 T cell subsets play an important role in Multiple Sclerosis (MS). Interleukin-27 (IL-27) suppresses Th (Th1, Th2 and Th17) cells and dampens autoimmunity and tissue inflammation by promoting the generation of Type 1 regulatory T cells (Tr1). Objective: To identify the relative levels of IL-27 and IL-17A in MS disease. Method: In a case-control study, venous blood was collected from forty MS patients and forty-three healthy subjects as control group. Serum levels of IL-27 and IL-17A were measured by ELISA method. Results: A significant difference between serum IL-17A concentration in patients (120.68 ± 209.85 pg/ml) and control group (67.26 ± 117.76 pg/ml, p=0.016) was found. Serum IL-27 levels of the MS patients (159.7 ± 581.4 pg/ml) were significantly lower than control subjects (180.35 ± 507.84 pg/ml, p=0.001). Conclusion: Our findings show decreased levels of IL-27 against increasing IL-17A levels in patients group which may suggest the suppressive role of IL-27 on inflammatory process of MS