Estrogen receptor-β signaling modulates epithelial barrier function

Looijer-van Langen M, Hotte N, Dieleman LA, Albert E, Mulder C, Madsen KL. Estrogen receptor-beta signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 300: G621-G626, 2011. First published January 20, 2011; doi: 10.1152/ajpgi.00274.2010.-Impaired epithelial barrier function and estrogens are recognized as factors influencing inflammatory bowel disease (IBD) pathology and disease course. Estrogen receptor-beta (ER beta) is the most abundant estrogen receptor in the colon and a complete absence of ER beta expression is associated with disrupted tight-junction formation and abnormal colonic architecture. The aim of this study was to determine whether ER beta signaling has a role in the maintenance of epithelial permeability in the colon. ER beta mRNA levels and colonic permeability were assessed in IL-10-deficient mice and HLA-B27 rats by RT-PCR and Ussing chambers. ER beta expression and monolayer resistance were measured in HT-29 and T84 colonic epithelial monolayers by RT-PCR and electric cell-substrate impedance sensing. The effect of 17 beta-estradiol and an estrogen agonist [diarylpropionitrile (DPN)] and antagonist (ICI 182780) on epithelial resistance in T84 cells was measured. Expression of ER beta and proinflammatory cytokines was investigated in colonic biopsies from IBD patients. Levels of ER beta mRNA were decreased, whereas colonic permeability was increased, in IL-10-deficient mice and HLA-B27 transgenic rats prior to the onset of colitis. T84 cells demonstrated higher resistance and increased levels of ER beta mRNA compared with HT-29 cells. 17 beta-estradiol and DPN induced increased epithelial resistance in T84 cells, whereas an ER beta blocker prevented the increased resistance. Decreased ER beta mRNA levels were observed in colonic biopsies from IBD patients. This study suggests a potential role for ER beta signaling in the modulation of epithelial permeability and demonstrates reduced ER beta mRNA in animal models of colitis and colon of patients with inflammatory bowel disease.