Differential expression of liver interleukin-6 receptor-alpha in female versus male ethanol-consuming rats.
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.
Gallucci
Randle M
RM
Department of Pharmaceutical Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA. randy-gallucci@ouhsc.edu
Sloan
Dusti K
DK
O'Dell
Sijy J
SJ
Reinke
Lester A
LA
D000428:Alcohol Drinking / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics
D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D000431:Ethanol