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Differential Expression of Liver Interleukin‐6 Receptor‐α in Female Versus Male Ethanol‐Consuming Rats
Author(s) -
Gallucci Randle M.,
Sloan Dusti K.,
O'Dell Sijy J.,
Reinke Lester A.
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000118316.20560.0d
Subject(s) - alcoholic liver disease , endocrinology , medicine , proinflammatory cytokine , western blot , hepatocyte , receptor , inflammation , biology , interleukin , cytokine , gene expression , liver injury , messenger rna , liver regeneration , stat3 , apoptosis , gene , biochemistry , microbiology and biotechnology , regeneration (biology) , cirrhosis , in vitro
A bstract : 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.