Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts |
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Authors: | Takuma Tsuzuki Wada Yasuto Araki Kojiro Sato Yoshimi Aizaki Kazuhiro Yokota Yoon Taek Kim Hiromi Oda Riki Kurokawa Toshihide Mimura |
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Institution: | 1. Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan;2. Division of Project, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan;3. Department of Orthopaedic Surgery, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan;4. Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan |
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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. |
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Keywords: | RA rheumatoid arthritis OA osteoarthritis SFs synovial fibroblasts IL-6 interleukin-6 TNF-α tumor necrosis factor α H3ac acetylation of histone H3 H3K4me3 tri-methylation of histone H3 lysine 4 HAT histone acetyltransferase |
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