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Published on: May 25, 2017
Estrogen suppresses heptatic IκB expression during short-term alcohol exposure
Eric G Lee1, Bethany M Mickle-Kawar, Lester A Reinke
1Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Objective:
To assess the effects of sex steroids on hepatic inflammatory pathways in short-term chronically ethanol-fed rats.
Methods:
Ovariectomized female Wistar rats (8-12 weeks old, n = 8 per treatment group) were implanted with osmotic pumps releasing 17β-estradiol (20 μg/24 h) or testosterone (25 μg/24 h) and fed liquid diets with or without ethanol (8 % w/v) for two weeks. Hepatic expression of IκBα/β, TNF-α, and IL-6 mRNA was examined by real-time PCR. Liver (nuclear) NFκB, IκBα and β, IL-6, and IL-6Rα protein expression was examined by enzyme-linked immunosorbent assay (ELISA) or Western blot.
Results:
Estrogen alone induced greater steatosis, NFκB translocation, TNF-α mRNA, as well as IL-6, and IL-6R protein. Alcohol consumption along with estrogen treatment further increased steatosis, NFκB translocation, TNF-α mRNA, and IL-6 protein. Conversely, neither estrogen nor ethanol consumption induced IκBα or IκBβ mRNA or protein expression, while testosterone robustly induced these inhibitory proteins regardless of treatment.
Conclusions:
Estrogen exposure enhances alcohol-induced liver inflammation, and the anti-inflammatory effects of testosterone in the liver might be related to induction of IκB. Elevated inflammation in response to estrogen may overwhelm the regenerative influence of IL-6 in liver, leading to increased steatosis and greater liver damage.
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