Immunoregulatory effects of glutathione during mesenchymal stem cell differentiation to hepatocyte-like cells

The role of mesenchymal stem cell in cellular therapy is the subject of interest for many researchers. The differentiation potential of MSCs and abilities in modulations of the recipient's immune system makes them important cells in tissue regenerative studies. MSCs by releasing the proinflammatory cytokines play important role in immunomodulatory systems; however the signaling pathways for releasing of these mediators are not well understood. Glutathione has been shown to play a role in modulation of cytokines in hepatogenic differentiation. In the current study we aimed to investigate the effects of buthionine sulfoximine [BSO, inhibitor for glutathione synthesis] and N-acetylecystin [NAC, an inhibitor for ROS generation] on proinflammatory cytokines production in a hepatogenic differentiation model. BSO and NAC significantly decreased IL-6 and TNF-alpha levels at 14 days of differentiation, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation. Moreover, intracellular glutathione level during the differentiation was depleted. Our current study suggests a novel role of GSH as an immunopharmacological regulatory molecule during hepatogenic differentiation. Finally, this information may shed some light on the understanding of MSCs responses in transplantation and cell therapy in diseases such as chronic hepatic diseases.

Lack of association between interleukin 12 C[-1188]A polymorphism and irritable bowel syndrome

Irritable Bowel Syndrome [IBS] is a functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. This study was performed to investigate the important role of interleukin-12 [IL-12] in intestinal inflammation. For this study seventy one patients with IBS and 140 controls were investigated. The allele and genotype frequencies of IL-12 C[-1188]A were determined using polymerase chain reaction with sequence-specific primers. The allele A was more common that the allele C in both groups of patients and controls. There was not any significant difference on IL-12 alleles and genotypes between patients and controls. The AA genotype was the most common genotypes, which was seen in 57.4% of the patients and 51.4% of the controls [p=0.53]. Although frequency of the CC genotype in the control group was lower than the patient group, this difference was not significant [5.7% vs. 11.5%, respectively, p=0.16]. Considering the lack of association between IL-12 C[-1188]A polymorphism and IBS, this cytokine gene polymorphism may not have significant role in the pathophysiology of disease