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Biochem Biophys Res Commun. 2014 Feb 21;444(4):682-6. doi: 10.1016/j.bbrc.2014.01.195. Epub 2014 Feb 7.

Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts.

Author information

1
Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; Division of Project, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan.
2
Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; Division of Project, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan. Electronic address: arakiya@saitama-med.ac.jp.
3
Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
4
Department of Orthopaedic Surgery, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
5
Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan.

Abstract

Accumulating evidence indicates that epigenetic aberrations have a role in the pathogenesis of rheumatoid arthritis (RA). However, reports on histone modifications are as yet quite limited in RA. Interleukin (IL)-6 is an inflammatory cytokine which is known to be involved in the pathogenesis of RA. Here we report the role of histone modifications in elevated IL-6 production in RA synovial fibroblasts (SFs). The level of histone H3 acetylation (H3ac) in the IL-6 promoter was significantly higher in RASFs than osteoarthritis (OA) SFs. This suggests that chromatin structure is in an open or loose state in the IL-6 promoter in RASFs. Furthermore, curcumin, a histone acetyltransferase (HAT) inhibitor, significantly reduced the level of H3ac in the IL-6 promoter, as well as IL-6 mRNA expression and IL-6 protein secretion by RASFs. Taken together, it is suggested that hyperacetylation of histone H3 in the IL-6 promoter induces the increase in IL-6 production by RASFs and thereby participates in the pathogenesis of RA.

KEYWORDS:

Curcumin; Epigenetics; Histone modifications; Interleukin-6; Rheumatoid arthritis; Synovial fibroblasts

PMID:
24513290
DOI:
10.1016/j.bbrc.2014.01.195
[Indexed for MEDLINE]
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