17β-estradiol reduces inflammation and modulates antioxidant enzymes in colonic epithelial cells

Abstract

Background/Aims: Estrogen is known to have protective effect in colorectal cancer development. The aims of this study are to investigate whether estradiol treatment reduces inflammation in CCD841CoN, a female human colonic epithelial cell line and to uncover underlying mechanisms of estradiol effects. Methods: 17 beta-Estradiol (E2) effect was measured by Western blot after inducing inflammation of CCD841CoN by tumor necrosis factor alpha (TNF-alpha). Expression levels of estrogen receptor alpha (ER alpha) and beta (ER beta), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappa B), heme oxygenase-1 (HO-1), and NAD(P)H-quinone oxidoreductase-1 (NQO-1) were also evaluated. Results: E2 treatment induced expression of ERO but did not increase that of ER alpha. E2 treatment for 48 hours significantly elevated the expression of anti-oxidant enzymes, HO-1 and NQO-1. TNF-alpha treatment significantly increased the level of activated NF-kappa B (p < 0.05), and this increase was significantly suppressed by treatment of to nM of E2 (p < 0.05). E2 treatment ameliorated TNF-alpha-induced COX-2 expression and decrease of HO-1 expression. 4-(2-phenyl-5,7-bis(trifluoromethyl) pyrazolo(1,5-a)pyrimidin-3-yl)phenol (PHTPP), antagonist of ER beta, removed the inhibitory effect of E2 in the TNF-alpha-induced COX-2 expression (p = 0.05). Conclusions: Estrogen seems to inhibit inflammation in female human colonic epithelial cell lines, through down-regulation of NF-kappa B and COX-2 expression and induction of anti-oxidant enzymes such as HO-1 and NQO-1.