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

作者：Wada Takuma Tsuzuki; Araki Yasuto^*; Sato Kojiro; Aizaki Yoshimi; Yokota Kazuhiro; Kim Yoon Taek; Oda Hiromi; Kurokawa Riki; Mimura Toshihide

来源：Biochemical and Biophysical Research Communications, 2014, 444(4): 682-686.

DOI：10.1016/j.bbrc.2014.01.195

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

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.

• 出版日期2014-2-21