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Estrogen suppresses heptatic IκB expression during short-term alcohol exposure

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Abstract

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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Acknowledgments

This work was supported by NIH/NIAAA Grant R03AA015198.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA

    Eric G. Lee, Bethany M. Mickle-Kawar, Lester A. Reinke & Randle M. Gallucci

  2. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK, 73190, USA

    Randle M. Gallucci

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  1. Eric G. Lee
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  2. Bethany M. Mickle-Kawar
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  4. Randle M. Gallucci
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Correspondence to Randle M. Gallucci.

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Responsible Editor: Ian Ahnfelt-Rønne.

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Lee, E.G., Mickle-Kawar, B.M., Reinke, L.A. et al. Estrogen suppresses heptatic IκB expression during short-term alcohol exposure. Inflamm. Res. 61, 1053–1061 (2012). https://doi.org/10.1007/s00011-012-0497-8

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  • DOI: https://doi.org/10.1007/s00011-012-0497-8

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