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-6Ralpha) 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-6Ralpha expression. Analysis of rat liver samples showed that ethanol consumption significantly increased IL-6Ralpha 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-6Ralpha activation in these animals. Conversely, ethanol-consuming males displayed increased IkappaB 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.
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-6Ralpha) 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-6Ralpha expression. Analysis of rat liver samples showed that ethanol consumption significantly increased IL-6Ralpha 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-6Ralpha activation in these animals. Conversely, ethanol-consuming males displayed increased IkappaB 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.
Authors: Lerin R Luckett-Chastain; Michael A Ihnat; Bethany M Mickle-Kawar; Randle Michael Gallucci Journal: J Interferon Cytokine Res Date: 2012-02-07 Impact factor: 2.607
Authors: Nympha B D'Souza El-Guindy; Elizabeth J Kovacs; Philippe De Witte; Claudia Spies; John M Littleton; Willem J S de Villiers; Amanda J Lott; Timothy P Plackett; Nadine Lanzke; Gary G Meadows Journal: Alcohol Clin Exp Res Date: 2010-06-25 Impact factor: 3.455