%0 Journal Article
%T Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis
%A Tomoko Kawabata
%A Keiichiro Nishida
%A Koji Takasugi
%A Hiroko Ogawa
%A Kenei Sada
%A Yasutaka Kadota
%A Junko Inagaki
%A Satoshi Hirohata
%A Yoshifumi Ninomiya
%A Hirofumi Makino
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar3071
%X HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNF¦Á) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNF¦Á on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting.Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNF¦Á. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNF¦Á mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNF¦Á significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs.Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNF¦Á stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors.Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial tissues in multiple joints that leads to bone and joint destruction. Recent clinical application of biologic agents targeted to inflammatory cytokines including tumor necrosis factor ¦Á (TNF¦Á) or interleukin-1¦Â (IL)-1¦Â dramatically changed the treatment strategy for RA. These molecular therapies of RA are more effective than the conventional disease-modifying anti-rheumatic drugs (DMARDs), and can even stop the destructive process in some RA patients [1]. Neverthel
%U http://arthritis-research.com/content/12/4/R133