NFkB and IkB expression are modulated by sex steroids during alcohol liver inflammation (93.24)

Abstract

Abstract Women are more susceptible to alcoholic liver disease (ALD) than men. The release of cytokines from Kupffer cells during inflammation is associated with the pathogenesis of ALD, and chronically ethanol fed female rats express cytokine mediators differently than male counterparts. Differences in inflammatory gene expression in females may have a role in gender related ALD pathology. This study examines the effects of sex steroids on the NFkB and IL-6 pathways in chronically ethanol fed rats. Ovarectomized, female, Wistar rats implanted with osmotic pumps releasing estrogen or testosterone were fed liquid diets with and without ethanol for two and four weeks. Estrogen receiving animals had lower mRNA expression of IL-6Rα, SOCS-3, PIAS-3, C/EBPβ, IkBα, and IkBβ at 2 weeks with little difference observed at 4 weeks. Ethanol consumption induced lower mRNA expression of IL-6Rα, PIAS-3, IkBα, and IkBβ in both testosterone and estrogen receiving animals with the lowest levels consistently observed in the estrogen group. Nuclear NFkB was greatest in the estrogen groups and lowest in the ethanol consuming testosterone group. IkBα protein expression was greatest in the estrogen receiving groups. The combined effects of estrogen and ethanol resulted in the lowest mRNA expression and highest NFkB and IkBα protein expression. Our data suggest that testosterone and estrogen distinctively affect NFkB, IkBα, and IL-6R expression and function and the effect of testosterone may be protective in ALD. Funded by NIH/NIAAA grant R03AA015198