Effect of sitagliptin on depression in male wistar rats

Background: Growing evidence supports relationship between depression and inflammation. The hypothesis of involvement of inflammatory pathways in depression is supported by the findings of increased levels of proinflammatory cytokines. So, we decided to evaluate the effect of sitagliptin on depression using forced swim test (FST) and possible effects of sitagliptin on serum oxidative stress markers and cytokine gene expression in rat hippocampus.Methods: FST model was used to evaluate antidepressant effect in male wistar rats. Rats in group I (control group) were given normal saline, group II (standard group) were given fluoxetine, group III and IV (test groups) were given sitagliptin 5 mg/kg and sitagliptin 9 mg/kg respectively. All the drugs in all groups were given per orally. At the end, animals were sacrificed and blood was collected. Hippocampus of rat brain was dissected out. Serum oxidative stress markers and hippocampal pro inflammatory cytokine gene expression analysis was carried out.Results: Sitagliptin 5 mg/kg and 9 mg/kg showed reduction in depressive symptoms and hippocampal cytokine gene expression in comparison to control. In case of serum oxidative stress markers, there was statistically significant reduction in nitric oxide levels with stagliptin 9 mg/kg. Although there was a decrease in the levels of catalase and increase in the levels of glutathione with standard and test groups, the results were not statistically significant.Conclusions: The present study showed significant antidepressant effect activity of standard and test groups. Hence, further research should be carried out to substantiate above results.

Quantification of bovine cytokine gene expression using real-time RT-PCR methodology

T cells produce cytokines that affect host response to infection. This paper reports real-time RT-PCR conditions and validation steps for accurate quantification of Bos indicus cytokines, interleukin (IL)-2, IL-4, IL-8, IL12p-35, IL-13, tumoral necrosis factor (TNF)-alpha, interferon (IFN)-gamma, monocyte chemoattractant proteins (MCP)-1 and MCP-2, and the glycoprotein mucin (MUC)-1 in two groups of Nelore cattle, one resistant and the other susceptible to gastrointestinal nematode infections. RPL-19 was shown to be an ideal internal control gene, since its expression was constant across treatments and presented lower variation when compared to the GAPDH gene. The optimized conditions established in the present study can be used to determine the immune response of cattle under different experimental conditions, such as viral, bacterial and parasite infections.

Diagnosis of acute rejection by bile cytology and cytokine gene expression in rat liver transplantation model / 中国普通外科杂志

Objective To evaluate a reliable and noninvasive method for the diagnosis of acute rejection after liver transplantation.Methods The allogeneic, syngeneic and immunosuppresive models of orthotopic rat liver transplantation were established, and acute rejection was graded according to histopathological change. Bile was sent for cytology by microscopy,and the sequential detection of bile IL 2,IFN ?,IL 4 and IL 6 gene expression was performed at day 1 through day 7. Results The number of cells in bile was persistently high in allogeneic group,and blast and lymphocytes appeared in bile. IL 2 and IFN ? were detected only in allogeneic group,with a specificity of 70% and 67%(7/10 and 8/12),and a sensitivity of 39% and 44%(7/18 and 8/18)respectively.Conclusion Bile cytology and detection of IL 2 and IFN ?mRNA transcript are useful adjuvant diagnosic methods for acute rejection after liver transplantation.

The gene expression of cytokines in human tumor cell lines and specimens / 中国免疫学杂志

Objective:To study the role of IL-2,IL-4,IL-6,IL-10,IL-13 and IFN? in pathogenesis of human tumor.Methods:The gene expression of 6 cytokines in human tumor cell lines and specimens were detected by RT-PCR or RNA dot hybridization.Results: There were predominant expression of Th2 type cytokines in 183 different human tumor cell lines and specimens.The positive rate of IL-4,IL-6,IL-10,IL-13 .IFN? and IL-2 in 183 tumor cell lines and specimens were 65%,70.5%,83.6%,61.7%, 12.6% and 22.9%,respectively.Conclusion: Predominant expression of Th2 type cytokines play an important role in the pathogenesis and development of tumor, may be related to the evasion of tumor cells from immune surveillance.

Follow-up Study on Cell-mediated Immune Responses In Syphilitic Patients after in vitro Stimulation with the 47 kDa Antigen of Treponema pallidum / 대한면역학회지

Present study was aimed to investigate the immunological activities of the 47 kDa protein antigen from Treponema pallidum and conducted on 12 patients with syphilis (early, late, spontaneously healed, congenital and treated patients) followed by therapy. Peripheral blood mononuclear cells (PBMC) were obtained three times from each patient, on admission before the initiation of therapy, 1 and 6 months later. Eleven (96.7%) of the patients prior to therapy, showed depressed lymphoproliferative responses to the 47 kDa antigen (stimulation index <4) by 3H-thymidine incorporation assay. However, these T cell responses were seemed to be transient because most of the patients (63.6%) exhibited significantly higher lymphoproliferation after therapy. Before therapy, PBMC from spontaneously healed syphilis patients resulted in significantly increased gene expression of IFN- and proinflarnmatory cytokines, such as TNFa, IL-1B and IL-6, in response to the 47 kDa. Patients with late latent and late congenital syphilis exhibited lower IFN-r and proinflammatory cytokine mRNA expression than spontaneously healed syphilis group did. After therapy, IFN-r and proinflammatory cytokine mRNA expressions were gradually reduced in these groups. On the other hand, IFN- and proinflammatory cytokine gene expressions were considerably depressed in early syphilis patients, but these patients went on to express prominent IFN-r and proinflamrnatory cytokine mRNA with treatment. These data suggest that the pattern of cellular immune response in response to the 47 kDa antigen may be involved in the evaluation of the clinical course and outcome of syphilis followed by therapy.

Cell-mediated Immune Responses in Syphilitic Patients after In vitro Stimulation with the 47 kDa Antigen of Treponema pallidum / 대한면역학회지

Present study was aimed to investigate the immunological activities of the 47 kDa glycoprotein antigen from Treponema pallidum and conducted on 24 patients with syphilis, (early, late, spontaneously healed, congenital and treated patients) and on 17 normal healthy controls. Two opposite lymphoproliferative manifestations to the 47 kDa antigen were observed in syphilis patients by H-thymidine incorporation assay. Ten responders (stimulation index [Sl] >4) showed a 3-fold-higher proliferation than the nonresponders, and four of those responders were spontaneously healed patients. Furthermore, analysis by flow cytometry indicated a preferential expansion of CD4' T lymphocytes by the 47 kDa antigen in the spontaneously healed syphilis patients. Stimulation of PBMCs of spontaneously healed syphilis patients with the 47 kDa antigen for greater than 72 hrs resulted in piogressive augmentation of IFN-r, IL-2Ra and IL-2 mRNA measured by RT-PCR, but considerably reduced IL-4 and IL-10 mRNA expression. However, patients with late latent syphilis exhibited more increased IL-4 and IL-10 mRNA expressions in response to the 47 kDa antigen than spontaneously healed syphilis group. In contrast to other groups, when cultured with the 47 kDa antigen very low IFN-#y, IL-2Ra and IL-2 mRNA expressions were shown in early syphilis group. These data suggest that the Th1-predominant cellular responses induced by the 47 kDa antigen may be involved in the clinical outcome of syphilis and provide the immunologic basis for further functional studies regarding the role of the 47 kDa in the immunopathogenesis of syphilis.

Analysis of Cytokine Gene Expression in Thyroid Aspirates and Peripheral Blood Mononuclear Cell and in vitro Production of Interferon / 대한내분비학회지

Cytokine production was studied in thyroid fine needle aspirates and peripheral blood and the production of interferon-gamma by peripheral blood mononuclear cell(PBMC) culture in response to interleukin-2(IL-2) stimulation was also studied from patients with hyperthyroidism, non toxic goiter, thyroid nodule. The expression of glycer aldehyde 3-phosphate dehydrogenase(GAPDH), interleukin-1beta(IL-1beta), IL-2, interleukin-8(IL-8), platelet- derived growth factor-A(PDGF-A) and interferon-gamma(IFN-gamma) chain was assessed by RT-PCR(reverse transcriptase polymerase chain reaction) in fine needle aspirates of thyroid and peripheral blood mononuclear cell : the samples were obtained from 7 patients with hyperthyroidism, 6 patients with non toxic goiter, 7 patients with thyroid nodule. A dose of IL-2(25 U/ml) was utilized to induce IFN-gamma production by PBMC from all patients.The results were as follows:1) In case of cytokine expression of fine-needle aspirates, GAPDH and IL-1beta, IL-8 were expressed highly but IFN-gamma, IL-2 were not expressed in hyperthyroidism and non-toxic goiter, thyroid nodule. PDGF-A was expressed in hyperthyroidism and thyroid nodule but not in non toxic goiter. 2) In case of cytokine expression of PBMC, GAPDH, IL-1beta were expressed in hyperthyroidism and non toxic goiter, thyroid nodule and highly expressed after IL-2 stimulation than before. But PDGF-A was more expressed in non toxic goiter and thyroid nodule than hyperthyroidism. Also, IFN-gamma was less expressed in thyroid nodule than hyperthyroidism and non toxic goiter. 3) The incremental increase in IFN-gamma value in supernatants of PBMC culture was significantly higher in patients with non toxic goiter than that in PBMC from hyperthyroidism and thyroid nodule(p<0.05).Therefore it seems that the cytokine production was found in hyperthyroidism and non toxic goiter and thyroid nodule. There were variability in their distribution each other, in general, higher expressed in hyperthyroidism than non toxic goiter. And RT-PCR Method that employed should be sufficiently sensitive to permit the analysis of cytokine gene expression in fine needle aspiration biopsies from patients with thyroid disease.

Effects of sinomenine on IL- 1?, LL-8 gene expression of human peripheral blood / 中国免疫学杂志

Objective:To study the anti-inflammatory and anti-rheumatic mechanisms of sinomenine, a pure alkaloid extracted from the Chinese medical plant sinomeniuim acutum, on cytokines-related genes modulation. Methods: Cultured normal human peripheral blood mononuclear cytes(PBMIN) with sinomenine in vitro, isolated total RNA from different groups of treated and controlled cells to investigate the effects on mRNA expression of IL-1?, LL-8 with LPS stimulation by one-step and two-step RT-PCR techniques. Results: The results from the one-step RTPCR showed that the inhibition ratio on IL-l?mRNA expression in the group of mmol/L sinomenine was about( 15.7?5.52) % ; with two-step RT-PCR techneque demonstrated that the inhibition ratio of sinomenine in the group of sinomenine with the concentration of 1 mmol/L, 100 umol/L on IL-1?mRNA expression were ahout( 17.07 ? 7 .69)% ,(25 .99 ? .84)% respectively and the inhitition ratio in the group with sinomenine concentration of 1 mmol/L,100umol/L on IL-8mRNA expression were(2l.01 ?7.79)%,(16.04?7.55)% respectively .Conclusion: The therapeutic effects of sinomenine on rheumatoid arthritis(RA) may partially related to downregulating gene expression of IL-1?, IL-8 cytokines of the peripheral blood mononuclear cells.