Gut and Liver

The Korean Association for the Study of the Liver (대한간학회)
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Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

  • Song, Chin-Hee (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Kim, Nayoung (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Sohn, Sung Hwa (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Lee, Sun Min (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Nam, Ryoung Hee (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Na, Hee Young (Department of Pathology, Seoul National University Bundang Hospital) ;
  • Lee, Dong Ho (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Surh, Young-Joon (Tumor Microenvironment Global Core Research Center, Seoul National University College of Pharmacy)
  • Received : 2018.05.16
  • Accepted : 2018.09.12
  • Published : 2018.11.15
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Abstract

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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