Korean J Intern Med.  2020 Mar;35(2):310-319. 10.3904/kjim.2018.098.

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

• Son HJ
• Kim N
• Song CH
• Lee SM
• Lee HN
• Surh YJ

• KMID: 2502017
• DOI: http://doi.org/10.3904/kjim.2018.098

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
17β-Estradiol (E2) effect was measured by Western blot after inducing inf lammation of CCD841CoN by tumor necrosis factor α (TNF-α). Expression levels of estrogen receptor α (ERα) and β (ERβ), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), heme oxygenase-1 (HO-1), and NAD(P)H-quinone oxidoreductase-1 (NQO-1) were also evaluated.
Results
E2 treatment induced expression of ERβ but did not increase that of ERα. E2 treatment for 48 hours significantly elevated the expression of anti-oxidant enzymes, HO-1 and NQO-1. TNF-α treatment significantly increased the level of activated NF-κB (p < 0.05), and this increase was significantly suppressed by treatment of 10 nM of E2 (p < 0.05). E2 treatment ameliorated TNF-α-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 ERβ, removed the inhibitory effect of E2 in the TNF-α-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-κB and COX-2 expression and induction of anti-oxidant enzymes such as HO-1 and NQO-1.

Keyword

Estrogens; Estrogen receptor beta; Inflammation; NF-kappa B; Heme oxygenase-1