Changes in genes methylation of the TLR pathway in livers of mice fed DDC

Abstract

BackgroundMallory‐Denk body (MDB) formation is a component of alcoholic and non alcoholic hepatitis. Proteins of the TLR pathway were shown to be involved in the formation of MDBs, in mice fed DDC. TLR genes are upregulated and SAMe supplementation prevents this up regulation and prevented the formation of MDBs.MethodDNA of livers from control mice, from mice fed DDC 10 weeks, refed 1 week with DDC and with DDC+SAMe were extracted and used to study the methylation pattern of genes involves in the TLR pathway. A PCR array was used to analyze it.ResultsUsing PCR array for the mouse TLR pathway (24 genes) were found whose the expression of IL12A was regulated by the methylation of its gene. DDC treatment reduced the methylation of the IL12A gene expression, with a similar level when DDC was refed. However, in the presence of SAMe, the intermediate level of methylation of IL12A was up regulated and the methylation of the promoter decreased compared to DDC refeeding or DDC 10 weeks.ConclusionIL12a is known to induce the production of IFNg by NK and LT. We showed in previous publication that IFNg is one of the major cytokines involved in the induction of MDB formation. The low expression of IL12A associated with the intermediate methylation of its promoter could explain one step in the mechanism which leads to the formation of MDBs. Supported by NIAAA PA50‐011999.