Histone deacetylase inhibitors suppress rheumatoid arthritis fi broblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay

Background Histone deacetylase inhibitors (HDACi) display potent therapeutic effi cacy in animal models of arthritis and suppress infl ammatory cytokine production in rheumatoid arthritis (RA) synovial macrophages and tissue. Objectives To determine the molecular mechanisms contributing to the suppressive effects of HDACi on RA synovial cell activation, using interleukin 6 (IL-6) regulation as a model. stability of IL-6 mRNA in FLS and macrophages. Conclusions Our study identifi es a novel, shared molecular mechanism by which HDACi can disrupt infl ammatory cytokine production in RA synovial cells, namely the promotion of mRNA decay, and suggests that targeting HDAC activity may be clinically useful in suppressing infl ammation in RA.

[1]  L. Joosten,et al.  Inhibition of HDAC Activity by ITF2357 Ameliorates Joint Inflammation and Prevents Cartilage and Bone Destruction in Experimental Arthritis , 2011, Molecular medicine.

[2]  N. Damjanov,et al.  HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis , 2011, Molecular medicine.

[3]  P. François,et al.  Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. , 2011, Blood.

[4]  E. Verdin,et al.  Regulatory signal transduction pathways for class IIa histone deacetylases. , 2010, Current opinion in pharmacology.

[5]  R. Gay,et al.  Epigenetics and rheumatoid arthritis: the role of SENP1 in the regulation of MMP-1 expression. , 2010, Journal of autoimmunity.

[6]  S. Krausz,et al.  Histone Deacetylase Inhibitors Suppress Inflammatory Activation of Rheumatoid Arthritis Patient Synovial Macrophages and Tissue , 2010, The Journal of Immunology.

[7]  X Chen,et al.  HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability , 2010, Oncogene.

[8]  G. Firestein,et al.  Fibroblast‐like synoviocytes: key effector cells in rheumatoid arthritis , 2010, Immunological reviews.

[9]  Yuan Shen,et al.  Deacetylase inhibition increases regulatory T cell function and decreases incidence and severity of collagen-induced arthritis. , 2009, Experimental and molecular pathology.

[10]  Patrick G. Shaw,et al.  Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells , 2009, Breast Cancer Research and Treatment.

[11]  N. Nishimoto,et al.  Clinical value of blocking IL-6 receptor , 2009, Current opinion in rheumatology.

[12]  Haruki Nakamura,et al.  Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay , 2009, Nature.

[13]  P. Tak,et al.  Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on? , 2008, Arthritis research & therapy.

[14]  J. Keen,et al.  Trichostatin A and 5 Aza-2′ deoxycytidine decrease estrogen receptor mRNA stability in ER positive MCF7 cells through modulation of HuR , 2008, Breast Cancer Research and Treatment.

[15]  C. Lowenstein,et al.  Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling , 2008, The Journal of experimental medicine.

[16]  Oliver Distler,et al.  Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts , 2007, Arthritis Research & Therapy.

[17]  H. Moch,et al.  Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients. , 2007, Arthritis and rheumatism.

[18]  R. Baron,et al.  Anti‐rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen‐induced arthritis in rodents , 2007, British journal of pharmacology.

[19]  Jeffrey Wilusz,et al.  The highways and byways of mRNA decay , 2007, Nature Reviews Molecular Cell Biology.

[20]  G. Fantuzzi,et al.  Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice1 , 2006, The Journal of Immunology.

[21]  C. Benz,et al.  Rapid alteration of microRNA levels by histone deacetylase inhibition. , 2006, Cancer research.

[22]  E. Seto,et al.  Acetylation and deacetylation of non-histone proteins. , 2005, Gene.

[23]  R. Gay,et al.  Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis , 2005, Annals of the rheumatic diseases.

[24]  K. Subbaramaiah,et al.  Histone Deacetylase Inhibitors Suppress the Induction of c-Jun and Its Target Genes Including COX-2* , 2005, Journal of Biological Chemistry.

[25]  P. Maslak.  Erythrocyte Sedimentation Rate. , 2005, British medical journal.

[26]  Masahiro Yamamura,et al.  Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1/Cip1) expression. , 2004, Arthritis and rheumatism.

[27]  P. Tak,et al.  Activation of the STAT1 pathway in rheumatoid arthritis , 2004, Annals of the rheumatic diseases.

[28]  Ae-June Wang,et al.  A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[29]  A. V. van Kuilenburg,et al.  Histone deacetylases (HDACs): characterization of the classical HDAC family. , 2003, The Biochemical journal.

[30]  W. Greene,et al.  Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF‐κB , 2002, The EMBO journal.

[31]  G. Fantuzzi,et al.  The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Wolffe,et al.  Chromatin remodeling and transcriptional activation: the cast (in order of appearance) , 2001, Oncogene.

[33]  E. Vellenga,et al.  Extracellular-regulated kinase 1/2, Jun N-terminal kinase, and c-Jun are involved in NF-kappa B-dependent IL-6 expression in human monocytes. , 1999, Journal of immunology.

[34]  F. Breedveld,et al.  Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. , 1997, Arthritis and rheumatism.

[35]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[36]  P. Tak,et al.  Function of histone deacetylase inhibitors in inflammation. , 2011, Critical reviews in immunology.

[37]  那須 義久.  Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model , 2008 .

[38]  Claudia Mauri,et al.  Cells of the synovium in rheumatoid arthritis , 2007 .

[39]  佐藤栄一.  DAS（disease activity score) , 2005 .

[40]  W. Greene,et al.  Shaping the nuclear action of NF-kappaB. , 2004, Nature reviews. Molecular cell biology.

[41]  C. Sardet,et al.  Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65. , 2003, The Journal of biological chemistry.

[42]  W. Greene,et al.  Duration of nuclear NF-kappaB action regulated by reversible acetylation. , 2001, Science.

[43]  C. Werning.  [Rheumatoid arthritis]. , 1983, Medizinische Monatsschrift fur Pharmazeuten.