The expression analysis of IL-6, IL-18, IL-21, IL-23, and TGF-ß mRNA in the nasal mucosa of patients with Allergic rhinitis.

Background: The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR). Objective: This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-ß in nasal biopsies in AR patients and evaluate its correlation with the severity of AR. Material and method: The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-ß was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured. Result: The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-ß declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups. Conclusion: We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation.

The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1ß protein.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1ß and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1ß was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1ß in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1ß protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1ß and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1ß mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1ß and increasing IL-11 production.

Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat.

Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rats.

The Role of Inflammatory Cytokines in Creating T Cell Exhaustion in Cancer.

Secreted inflammatory cytokines are considered as critical mediators in the tumor microenvironment. Cancer cells play a significant role in the differentiation of effector T cells to exhausted T cells through mediator production. Effector T cells that undergo tumor microenvironment become terminally differentiated into exhausted T cells. These changes create an opportunity for tumorigenesis and invasion of cancer cells. Despite having some characteristics of effector T cells, the exhausted T cells lose their antitumor properties. In this article, the phenotypes and function of exhausted T cells were reviewed and the expression pattern of inflammatory cytokines in tumor tissues and peripheral blood of cancer patients were described. Additionally, the effects of inflammatory cytokines on intracellular factors and signals of T lymphocyte cells were explained. In conclusion, the authors referred to probable approaches that could be used to improve the antitumor activity of T cells and intervention into T cell exhaustion.

The expression analysis of Fra-1 gene and IL-11 protein in Iranian patients with ulcerative colitis.

BACKGROUND: Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression. MATERIALS AND METHODS: We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11. RESULTS: An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group. CONCLUSION: Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.