The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma.Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53.Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52±47.62 pg/ml vs. mean 101.91±22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma.The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.

No abstract

No abstract

Aims/Hypothesis: Galectin 3 appears to play a proinflammatory role in several inflammatory and autoimmune diseases. Also, there is evidence that galectin 3 plays a role in both type-1 and type-2 diabetes. During obesity, hematopoietic cell-derived galectin 3 induces insulin resistance. While the role of galectin 3 expressed in islet-invading immune cells in both type-1 and type-2 diabetes has been studied, the importance of the expression of this molecule on the target pancreatic β cells has not been defined. Methods:To clarify the role of galectin 3 expression in β cells during obesity-induced diabetogenesis, we developed transgenic mice selectively overexpressing galectin 3 in β cells and tested their susceptibility to obesity-induced type-2 diabetes. Obesity was induced with a 16-week high-fat diet regime. Pancreatic β cells were tested for susceptibility to apoptosis induced by non-esterified fatty acids and cytokines as well as parameters of oxidative stress.Results: Our results demonstrated that overexpression of galectin 3 increases β-cell apoptosis in HFD conditions and increases the percentage of proinflammatory F4/80 + macrophages in islets that express galectin 3 and TLR4. In isolated islets, we have shown that galectin 3 overexpression increases cytokine and palmitate-triggered β-cell apoptosis and also increases NO 2− -induced oxidative stress of β cells. Also, in pancreatic lymph nodes, macrophages were shifted toward a proinflammatory TNF-α-producing phenotype.Conclusions/Interpretation: By complementary in vivo and in vitro approaches, we have shown that galectin 3-overexpression facilitates β-cell damage, enhances cytokine and palmitate-triggered β-cell apoptosis, and increases NO 2− -induced oxidative stress in β cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic β cells affects the metabolism of glucose and glycoregulation in mice on a high-fat diet, affecting both fasting glycemic values and glycemia after glucose loading.

Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Prevention of type 1 diabetes requires early intervention in the autoimmune process against beta-cells of the pancreatic islets of Langerhans, which is believed to result from disordered immunoregulation. CD4+Foxp3+ regulatory T cells (Tregs) participate as one of the most important cell types in limiting the autoimmune process. The aim of this study was to investigate the effect of exogenous IL-33 in multiple low dose streptozotocin (MLD-STZ) induced diabetes and to delineate its role in the induction of protective Tregs in an autoimmune attack. C57BL/6 mice were treated i. p. with five doses of 40 mg/kg STZ and 0.4 μg rIL-33 four times, starting from day 0, 6, or 12 every second day from the day of disease induction. 16 weeks old NOD mice were treated with 6 injections of 0.4 μg/mouse IL-33 (every second day). Glycemia and glycosuria were measured and histological parameters in pancreatic islets were evaluated at the end of experiments. Cellular make up of the pancreatic lymph nodes and islets were evaluated by flow cytometry. IL-33 given simultaneously with the application of STZ completely prevented the development of hyperglycemia, glycosuria and profoundly attenuated mononuclear cell infiltration. IL-33 treatment was accompanied by higher number of IL-13 and IL-5 producing CD4+ T cells and increased presence of ST2+Foxp3+ regulatory T cells in pancreatic lymph nodes and islets. Elimination of Tregs abrogated protective effect of IL-33. We provide evidence that exogenous IL-33 completely prevents the development of T cell mediated inflammation in pancreatic islets and consecutive development of diabetes in C57BL/6 mice by facilitating the induction Treg cells. To extend this finding for possible relevance in spontaneous diabetes, we showed that IL-33 attenuate insulitis in prediabetic NOD mice.

Objective: Th e aim of our study was to establish a correlation between pseudoexfoliation and its systemic manifestation. Findings: Pseudoexfoliation syndrome is an agerelated systemic disorder that leads to the overproduction and accumulation of the pseudoexfoliated materials in the visceral organs and in the eye. Many vascular diseases are closely related with pseudoexfoliation manifestations. Our results indicated that there were no statistically significant diff erences (p>0.05) among patients regarding the presence of hypertension in all groups: PEX glaucoma - 45% (9 patients); PEX syndrome- 40% (8 patients); and control groups- 35% (7 patients). Ischemic heart disease was statistically significant present in the sPEX syndrome- 20% (5 patients) and PEX glaucoma- 25% (5 patients) patient groupss, in comparison with those of the control group-10%, (p<0.05). Aortic aneurism was statistically significant present in patients with PEX (syndrome-5% or glaucoma-15%), compared to those in the control group, which included no patients with aneurisms, (p<0.05). Our results indicated that a statistically significant number of patients with aneurism were in the group of patients who developed PEX glaucoma (p<0.05). Cerebrovascular diseases were detected in all groups of patients, but a significant decrease in this metric was noted in the control group- 5% (2 patients), compared with patients with PEX syndrome- 15% and PEX glaucoma-25%, (p<0.05). Hearing loss, as a concomitant sign of PEX manifestation, was recorded in all patients, but in the group with PEX (syndrome-55% or glaucoma-75%), these results showed a statistically significant increase (p<0.05) in comparison with those of patients in the control group (10%). Among the patients with PEX (syndrome and glaucoma), there were no statistically significant diff erences in the selected categories of systemic manifestations (p<0.05). Th is result indicates that the main risk for systemic manifestation is the presence of PEX and that other ocular and vascular complications are, in fact, consequences of PEX. Conclusion: Pseudoexfoliation is strongly related to systemic vascular disturbances. A detailed examination of patients with PEX by specialists in internal disease or by neurologists should be performed. Such recommended examinations can be helpful in the prevention of diff erent vascular diseasess among patients with PEX, especially atthose in the early stages.

Background: The purpose of this study is to reveal the participation of different regulatory cytokines within the process of pseudoexfoliation (PEX). Methods: Our study included 140 patients referred to cataract surgery with early and late stage of pseudoexfoliation syndrome (XFS) or pseudoexfoliation glaucoma (XFG). Humor and serum levels of cytokines: transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), IL-8 and interferon-inducible T cell alpha chemoattractant (ITAC) were measured in a sample using high sensitivity enzyme-linked immunoabsorbent assay (ELISA) kit. Results: Our results indicate that profibrotic action induced by increasing TGF-β and PDGF locally activates fibrous tissue production in the early XFS with a prolonged effect of PDGF (late XFS) and finally (XFG stage) it is dominantly controlled by EGF and IGF. ITAC overrides angiogenetic effects of IL-8 in XFG. Conclusion: Based on our findings, local chronic inflammation in the eye is accompanied by the secretion of different profibrotic cytokines (TGF-β, PDGF, EGF, IGF, IL-8) without angiogenesis due to effects of ITAC.

No abstract