Higher Levels of Serum TLR2 and TLR4 in Patients with Hashimoto's Thyroiditis.

OBJECTIVE: Hashimoto's thyroiditis (HT) is an autoimmune disorder caused by the interaction between genes and environmental triggers. HT is the most common endocrine disorder, as well as the most common cause of hypothyroidism. Autoimmunity plays a crucial role in the pathogenesis of HT and recent studies suggest that Toll-like receptor (TLR) signals lead to increased inflammatory response. The aim of our study is to investigate whether TLR-2 and TLR-4 levels and gene polymorphisms contribute to the damaged immune response leading to HT. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, single-nucleotide polymorphisms (SNPs) of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile were studied in 100 patients with HT and 100 healthy controls. Also, we investigated serum levels of TLR-2 and TLR-4 in the immunopathogenesis of HT. TLR-2 and TLR-4 serum levels were found to be significantly higher in HT patients than the control group. However, no statistical significance was found between patient and control groups in terms of genotype frequencies and allele frequency distribution of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphisms. RESULT: TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphism do not appear to have a role in the development of HT disease. However, in our study, serum levels of TLR-2 and TLR-4 were found to be higher in HT patients than control groups. CONCLUSION: These findings suggest that TLR-2 and TLR-4 play an important role in the immunopathologic mechanism of disease by causing an increase in proinflammatory response.

Effects of humanin on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid in rats.

BACKGROUND/AIM: The excessive apoptosis of intestinal epithelial cells (IECs) partly accounts for the development of colonic inflammation and eventually results in ulcerative colitis (UC). Humanin, an endogenous anti-apoptotic peptide, has previously been shown to protect against Alzheimer's disease and a variety of cellular insults. The present study aimed to investigate the effects of glysin variant of humanin (HNG) on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Rats were divided into four groups as follows: Group 1 (n = 8): control; isotonic saline solution 0.1 ml/rat rectally, Group 2 (n = 8): TNBS colitis; 0.1 ml of a 2.5% (w/v) TNBS solution in 50% ethanol rectally, Group 3 (n = 8): 10 µM HNG, and Group 4 (n = 8): 20 µM HNG intraperitoneal (ip) on day 2 and 6 after rectal TNBS administration. Rats were sacrificed 7 days after the induction of colitis. Blood and tissue samples were harvested for biochemical and histopathological analysis. RESULTS: HNG treatment significantly ameliorated weight loss and macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and caspase-3 activities in group II in comparison to the group I. HNG treatment was associated with an inhibition of mRNA expression of TNF-α and IL-1ß, and a decrease in caspase-3 activities in colon tissues in group III and IV when compared to group II. CONCLUSION: The results of this study indicate that HNG treatment may exert beneficial effects in UC by decreasing inflammatory reactions and apoptosis.

Glutathione S-transferase GSTM 1, null genotype may be associated with susceptibility to age-related cataract.

BACKGROUND: Age-related cataract (ARC) is the leading cause of visual disability and reversible blindness all over the world. The different expressions of GST isozymes among animals may explain the variations in the cataract formation caused by oxidative stress. OBJECTIVES: In this study, we evaluated the distribution of GST gene polymorphisms in ARC patients and the possible associations between the presence of ARC and GST gene polymorphisms. MATERIAL AND METHODS: The epidemiological data was collected by a standard questionnaire and blood samples were obtained from 130 ARC patients and 159 healthy controls. Data about smoking habits of the groups was recorded. Real-time polymerase chain reaction-based methods were used to detect genetic polymorphisms. RESULTS: The GSTM 1 null genotype was found to carry an increased risk for developing ARC (OR: 1.84, 95% CI: 1.13-2.99). The frequency of the GSTT 1 null genotype was not significantly different among the ARC patients and the controls (OR: 1.0, 95% CI: 0.64-1.6). The GSTP 1 Val/Val genotype was also not significantly different among the ARC patients and control groups (OR: 1.06, 95% CI: 0.50-2.23). GSTM 1 null genotype was highly frequent in non-smokers (OR: 3.25, 95% CI: 1.66-6.35) and moderately frequent in smokers (OR: 2.50, 95% CI: 1.28-4.86). Also, carrying the combined genotypes of GSTM 1 null, GSTT 1 and GSTP 1 105-Val allele was seen to have an increased risk of developing ARC (OR: 2.91, 95% CI: 1.31-6.44). CONCLUSIONS: This data may provide evidence that GSTM 1 gene polymorphisms may be associated with genetic susceptibility to develop ARC. Larger studies are warranted to verify these findings.