The relationship between DNA methylation and histone deacetylation with HLA-B27 gene expression / 中华风湿病学杂志

ABSTRACT

Objective To study the relationship between DNA methylation inhibitor and histone deacetylase inhibitor (HDACI) with HLA-B27 gene expression. Methods Hela-HLA-B27 promoter stable cell line was developed as the first step and followed by detecting the effect of DNA methylation inhibitor(5-Aza-CdR) and HDACI. The synergetic effect of HDACI and cytokines as well as the effect of anti-TNF-α antibody, anti-IFN-β antibody, anti-IFN-γ antibody and Infiximab on HLA-B27 promoter activity were tested by measuring luciferase value. Then HLA-B27 mRNA expression level in CCL6-B27 genomic DNA stable cell line was measured by real-time PCR. Results Sodium butyrate(NaB) and valproic acid(VPA)could significantly up-regulate HLA-B27 promoter activity at 24 h (24.0±1.7) times, ( 17.4±2.2 ) times respectively,(P＜0.05). The synergetic effect between VPA with TNF-α, IFN-α, IFN-β, IFN-γ and PMA on HLA-B27 promoter activity was found. None of the antibody could inhibit the effect of HDACI. It also showed that NaB,TSA, VPA and 5-Aza-CdR could significantly increase HLA-B27 mRNA expression in CCL6-B27 stable cell line. Conclusion DNA methylation and HDACI can up-regulate HLA-B27 gene expression level.