Epigenetic regulation of pro-inflammatory cytokine genes in lipopolysaccharide -stimulated peripheral blood mononuclear cells from broilers.

ABSTRACT

Inflammatory response which can be mediated by inflammatory genes, can be induced by pathogenic microorganisms, be associated with enteric diseases and the loss of growth performance in broilers. The understanding of epigenetic regulation of inflammatory genes could help explain the response to infection of microorganisms and inhibit the reaction of inflammation in broilers. This study investigated the effect of histone acetylation by histone deacetylases (HDAC) inhibitors trichostain A (TSA) and DNA methylation by demethylation agent 5-Aza-2'-deoxycytidine (AZA) and methyl donor methionine (Met) and folic acid (FA) on the expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) from healthy broilers. The results showed that the mRNA expression of IL-1ß, IL-6 and TNF-α can be down-regulated by pre-treatment of TSA in LPS-stimulated broiler PBMC. The expression of pro-inflammatory cytokines related with the expression of HDAC7 and HDAC10 which can influence histone acetylation, and may also be affected by increasing the acetylation of non-histone proteins. The demethylation by AZA increased the expression of IL-6 and TNF-α in LPS-stimulated broiler PBMC. The addition of FA and Met decreased the expression of DNA methyltransferases (DNMT)1 and DNMT3a, while the Met also down-regulated the expression of IL-6 and TNF-α in LPS-stimulated cells. In addition, the Met administration increased the methylation of -191 CpG site (up-stream from transcription start site) of IL-6 and -419 CpG site of TNF-α. This study indicated that the expression of pro-inflammatory cytokines is regulated by protein acetylation. Demethylation also increased the expression of IL-6 and TNF-α, which can be regulated by Met through increasing the promoter methylation. These results may have implications for controlling inflammation by epigenetic regulation in broilers.