Open AccessEpac‐2 ameliorates spontaneous colitis in Il‐10 −/− mice by protecting the intestinal barrier and suppressing NF‐κB/MAPK signalling
Author(s) -
Song Xue,
Wen Hexin,
Zuo Lugen,
Geng Zhijun,
Nian Jing,
Wang Luyao,
Jiang Yifan,
Tao Jing,
Zhu Zihan,
Wu Xiaopei,
Wang Zhikun,
Zhang Xiaofeng,
Yu Liang,
Zhao Hao,
Xiang Ping,
Li Jing,
Shen Lin,
Hu Jianguo
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17077
Subject(s) - colitis , barrier function , intestinal permeability , mapk/erk pathway , inflammation , chemistry , inflammatory bowel disease , intestinal mucosa , cancer research , microbiology and biotechnology , kinase , immunology , biology , medicine , biochemistry , disease
Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn's disease (CD). A recent study indicated that Epac‐2 protected the intestinal barrier and had anti‐inflammatory effects. The present study examined the function of Epac‐2 in CD‐like colitis. Interleukin‐10 gene knockout ( Il ‐ 10 −/− ) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac‐2 agonists (Me‐cAMP) or Epac‐2 antagonists (HJC‐0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco‐2 and RAW 264.7 cell co‐culture system were used to analyse the effects of Epac‐2 on the cross‐talk between intestinal epithelial cells and inflammatory cells. Epac‐2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac‐2 activation also decreased Caco‐2 cell permeability in an LPS‐induced cell co‐culture system. Epac‐2 activation significantly suppressed nuclear factor (NF)‐κB/mitogen‐activated protein kinase (MAPK) signalling in vivo and in vitro. Epac‐2 may be a therapeutic target for CD based on its anti‐inflammatory functions and protective effects on the intestinal barrier.