Contents lists available at ScienceDirect Pathology - Research and Practice journal homepage: www.elsevier.com/locate/prp The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis Milad Sabzevary-Ghahfarokhi a , Mojtaba Shohan a , Hedayatollah Shirzad b, ⁎ , Ghorbanali Rahimian c , Amin Soltani d , Mahdi Ghatreh-Samani a , Fatemeh Deris e , Nader Bagheri a , Mohammedhadi Shafigh c , Kamran Tahmasbi f a Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran b Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran c Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran d Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran e Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran f Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran ARTICLE INFO Keywords: Oxidative stress Ulcerative colitis Nrf2 GST-A4 PRDX1 ABSTRACT Background: 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. Materials and methods: 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 in- flamed 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). Results: 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 ul- cerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression. Conclusion: 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 infl- ammation, 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. 1. Introduction The inflammatory bowel diseases (IBDs) has a wide range of asso- ciated disorders like ulcerative colitis (UC), characterised by recurrent chronic and incurable inflammatory conditions in the colon and rectum [1,2]. The interaction between genetic, nutritional and environmental agents initially presents more of the inflammatory conditions in UC [3]. Potentially, Inflammation damages the mucosal barrier function and amplify inflammatory response in the gastrointestinal tract [4]. Recent investigations have also indicated an association to exist between the degree of inflammation and the enhanced production of reactive oxygen species (ROS) such as nitric oxide and superoxide [5]. Under oxidative stress, nuclear factor erythroid 2 related factor 2 (Nrf2) can be released from Keap1 and translocates into the nucleus of cells [6]. The Nrf2 is mainly expressed in the nucleus of epithelial cells to conserve the intestinal integrity. The protective effects of Nrf2 in a chronic colitis mice caused lower expression of inflammatory cytokines [7]. Activated Nrf2 has the potential to suppress interleukin (IL)-17 expression in autoimmune disease [8]. In murine dextran sodium sulfate (DSS)-in- duced colitis, IL-17 augments inflamed intestinal by pro-inflammatory https://doi.org/10.1016/j.prp.2018.06.001 Received 12 April 2018; Received in revised form 27 May 2018; Accepted 6 June 2018 ⁎ Corresponding author. E-mail address: shirzad1951@yahoo.com (H. Shirzad). Abbreviations: ROS, reactive oxygen species; UC, ulcerative colitis; Nrf2, nuclear factor erythroid 2 related factor 2; IBD, inflammatory bowel diseases; DSS, dextran sodium sulfate; IL- 17, interleukin-17; APE1, apurinic/apyrimidinic endonuclease; PRDX1, peroxiredoxin-1; GST-A4, glutathione S-transferase-alpha4; 4-HNE, trans-4-hydroxy-2-nonenal; IEC, intestinal epithelial cells; COPD, chronic obstructive pulmonary disease; Hmox-1, heme oxygenase-1; RORct, retinoic orphan receptor gamma(t); MAPK, mitogen-activated protein kinase Pathology - Research and Practice 214 (2018) 1149–1155 0344-0338/ © 2018 Elsevier GmbH. All rights reserved. T