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

Pathol Res Pract. 2018 Aug;214(8):1149-1155. doi: 10.1016/j.prp.2018.06.001. Epub 2018 Jun 23.

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 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).

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 ulcerative 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 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.

Keywords: GST-A4; Nrf2; Oxidative stress; PRDX1; Ulcerative colitis.

MeSH terms

  • Adult
  • Antioxidants / metabolism
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology*
  • Female
  • Gene Expression Regulation / physiology
  • Glutathione Transferase / biosynthesis*
  • Humans
  • Interleukin-17 / biosynthesis*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / physiology
  • Peroxiredoxins / biosynthesis*

Substances

  • Antioxidants
  • IL17A protein, human
  • Interleukin-17
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • PRDX1 protein, human
  • Peroxiredoxins
  • Glutathione Transferase
  • leukotriene-C4 synthase