E ffect of deacetylase inhibitor VPA on polarization of macrophages / 中国免疫学杂志

ABSTRACT

Objective:By analyzing the effect of deacetylase inhibitors on macrophage polarization process of histone modification,and the influence of the process of macrophage polarization ,analysis deacetylase inhibitors whether have the effect on the activity of the macrophage polarization by altered histone modification of macrophages , in order to provide a new perspective for the treatment of autoimmune diseases .Methods:Using lipopolysaccharide ( LPS) and interferon-γ( IFN-γ) to stimulate J774.1 cells for 24 h,and interleukin-4 ( IL-4 ) to stimulate J774.1 cells for 24 h.And 2 mmol/L valproic acid ( VPA ) was added in the induction process.Collecting J774.1 cells,fluorescent quantitation PCR assay and ELISA assay was used for the detection of specific markers of gene expression in macrophage polarization , flow cytometry and immunofluorescence assay for the detection of histone modifications.Results:J774.1 cells were polarized into M1 macrophages which were stimulated by LPS and IFN-γfor 24 h;and also J774.1 cells were polarized into M2 macrophages which were stimulated by IL-4 for 24 h.The degree of acetylation of H 3K9 for M1 phenotype was increased after VPA treatment , the expression of interleukin-6 (IL-6 ) , inducible nitric oxide synthase ( iNOS ) , and chemotactic factor(CCL-2) was decreased,and the expression of CD86 was increased.The degree of acetylation of H3K9 for M1 phenotype was also increased after VPA treatment ,and also the expression of Arginase,Fizz-1,mannose receptor(CD 206) and Ym1 were increased.Conclusion:The polarization state of the macrophages and histone modification had a certain relevance .VPA could induce the transformation of M1 phenotype to M2 phenotype in the induction system of the M1 macrophages,however,the expression of specific genes in M1 phenotype was inhibited in the induction system of the M 2 macrophages.