Differential Expression of Liver Interleukin-6 Receptor-α in Female Versus Male Ethanol-Consuming Rats

Randle M. Gallucci, Dusti K. Sloan, Sijy J. O'Dell, Lester A. Reinke

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: It is well known that women are more susceptible to alcoholic liver disease (ALD) than men, and inflammation is thought to play a major role in alcohol-induced liver injury. Increased circulating levels of the proinflammatory cytokine interleukin (IL)-6 are a marker for serious ALD in humans. However, IL-6 also has protective effects, such as induction of liver regeneration and inhibition of hepatocyte apoptosis. Although the roles of IL-6 in ALD have begun to be established, little is known about the expression of its receptor (IL-6Rα) during chronic alcohol administration. Methods: Male and female rats were intragastrically fed ethanol or control isocaloric liquid diet for 2 and 4 weeks. Liver samples were collected, and gene expression was assessed by reverse transcription-polymerase chain reaction and Western blot. Results: Herein, we show clear gender differences in alcohol-induced liver IL-6Rα expression. Analysis of rat liver samples showed that ethanol consumption significantly increased IL-6Rα messenger RNA and protein expression in females as compared with similarly treated males after 2 and 4 weeks. Increased STAT3 phosphorylation in the livers of ethanol-consuming females also indicated greater IL-6Rα activation in these animals. Conversely, ethanol-consuming males displayed increased IκB messenger RNA and protein expression, which may inhibit IL-6R expression, compared with females. Conclusions: Given the association of inflammation with ethanol-induced liver damage, these data may offer insight into a possible mechanism by which females develop more severe ALD than males.

Original languageEnglish
Pages (from-to)365-373
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume28
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Gender
  • IκB
  • IL-6R
  • Inflammation
  • Liver

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