title: Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts.
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.
authors: 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.
authors: Takuma Tsuzuki
authors: TT
authors: Wada
authors: 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.
authors: Yasuto
authors: Y
authors: Araki
authors: Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
authors: Kojiro
authors: K
authors: Sato
authors: 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.
authors: Yoshimi
authors: Y
authors: Aizaki
authors: Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
authors: Kazuhiro
authors: K
authors: Yokota
authors: Department of Orthopaedic Surgery, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
authors: Yoon Taek
authors: YT
authors: Kim
authors: Department of Orthopaedic Surgery, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan.
authors: Hiromi
authors: H
authors: Oda
authors: Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan.
authors: Riki
authors: R
authors: Kurokawa
authors: 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.
authors: Toshihide
authors: T
authors: Mimura
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D003474:Curcumin / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D015850:Interleukin-6; D012333:RNA, Messenger; D051548:Histone Acetyltransferases; D003474:Curcumin
keywords: Curcumin; Epigenetics; Histone modifications; Interleukin-6; Rheumatoid arthritis; Synovial fibroblasts