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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Cells, Cultured
  • Curcumin / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Histone Acetyltransferases / antagonists & inhibitors
  • Histone Acetyltransferases / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-6 / genetics*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Promoter Regions, Genetic* / drug effects
  • RNA, Messenger / genetics
  • Synovial Membrane / cytology


  • Enzyme Inhibitors
  • Histones
  • Interleukin-6
  • RNA, Messenger
  • Histone Acetyltransferases
  • Curcumin