Mucosal gene expression changes induced by anti-TNF treatment in inflammatory bowel disease patients

Drug Dev Res. 2019 Sep;80(6):831-836. doi: 10.1002/ddr.21566. Epub 2019 Jul 19.

Abstract

In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.

Keywords: 5-ASA; Crohn disease; anti-TNF; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Colitis, Ulcerative / genetics*
  • Crohn Disease / genetics*
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Lipocalin-2 / genetics
  • Male
  • Mesalamine / pharmacology*
  • Middle Aged
  • Nitric Oxide Synthase Type II / genetics
  • Trefoil Factor-1 / genetics
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • LCN2 protein, human
  • Lipocalin-2
  • TFF1 protein, human
  • TNF protein, human
  • Trefoil Factor-1
  • Tumor Necrosis Factor-alpha
  • Mesalamine
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II