The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis

• Published in: Pathology, research and practice research and practice, 2018-08, Vol.214 (8), p.1149-1155
• Main Authors: Sabzevary-Ghahfarokhi, Milad, Shohan, Mojtaba, Shirzad, Hedayatollah, Rahimian, Ghorbanali, Soltani, Amin, Ghatreh-Samani, Mahdi, Deris, Fatemeh, Bagheri, Nader, Shafigh, Mohammedhadi, Tahmasbi, Kamran
• Format: Article
• Language: English
• Subjects: GST-A4; Nrf2; Oxidative stress; PRDX1; Ulcerative colitis
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2018.06.001

[Display omitted] The performance of Nrf2 is designed in colonic tissue of patients with UC. Environmental effects trigger innate immune system to produce ROS and inflammatory mediators. IL-17 can be released in response to Th-17 activation. phase II antioxidant genes such as PRDX1 and GST-A4 is induced as a result of the Nrf2 activation. Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1. A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR). In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression. Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC.