The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts

Annals of the Rheumatic Diseases

Volumn 75, Issue 2, 2016, Pages 422-429

  Klein, Kerstin ^a   Kabala, Pawel A ^b   Grabiec, Aleksander M ^b   Gay, Renate E ^a   Kolling, Christoph ^c   Lin, Lih Ling ^d   Gay, Steffen ^a   Tak, Paul P ^b,e,f   Prinjha, Rab K ^e   Ospelt, Caroline ^a   Reedquist, Kris A ^b  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

^c SCHULTHESS CLINIC   (Switzerland)

^d PFIZER INC   (United States)

^e GLAXOSMITHKLINE   (United Kingdom)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

7 (3,5 DIMETHYL 4 ISOXAZOLYL) 1,3 DIHYDRO 8 METHOXY 1 [1 (2 PYRIDINYL)ETHYL] 2H IMIDAZO[4,5 C]QUINOLIN 2 ONE; BRD2 PROTEIN, HUMAN; BRD3 PROTEIN, HUMAN; BRD4 PROTEIN, HUMAN; FUSED HETEROCYCLIC RINGS; IL6 PROTEIN, HUMAN; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; LIPOPOLYSACCHARIDE; MESSENGER RNA; MMP1 PROTEIN, HUMAN; MMP3 PROTEIN, HUMAN; NUCLEAR PROTEIN; PROTEIN SERINE THREONINE KINASE; RNA BINDING PROTEIN; STROMELYSIN; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR; TUMOR NECROSIS FACTOR ALPHA;

DRUG EFFECTS; ENZYMOLOGY; FIBROBLAST; GENE EXPRESSION; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; METABOLISM; OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; SYNOVIUM;

ARTHRITIS, RHEUMATOID; FIBROBLASTS; GENE EXPRESSION; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; IMMUNOHISTOCHEMISTRY; INTERLEUKIN-1BETA; INTERLEUKIN-6; INTERLEUKIN-8; LIPOPOLYSACCHARIDES; MATRIX METALLOPROTEINASE 1; MATRIX METALLOPROTEINASE 3; NUCLEAR PROTEINS; OSTEOARTHRITIS; PROTEIN-SERINE-THREONINE KINASES; RNA, MESSENGER; RNA-BINDING PROTEINS; SYNOVIAL MEMBRANE; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTORS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84954338878     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2014-205809     Document Type: Article

References (32)

1. Neumann E, Lefevre S, Zimmermann B, et al. Migratory potential of rheumatoid arthritis synovial fibroblasts: additional perspectives. Cell Cycle 2010;9:2286-91.
2. Klein K, Gay S. Epigenetic modifications in rheumatoid arthritis, a review. Curr Opin Pharmacol 2013;13:420-5.
3. Ospelt C, Reedquist KA, Gay S, et al. Inflammatory memories: is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis? Autoimmun Rev 2011;10:519-24.
4. Karouzakis E, Gay RE, Michel BA, et al. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2009;60:3613-22.
5. Nakano K, Whitaker JW, Boyle DL, et al. DNA methylome signature in rheumatoid arthritis. Ann Rheum Dis 2013;72:110-17.
6. Grabiec AM, Reedquist KA. The ascent of acetylation in the epigenetics of rheumatoid arthritis. Nat Rev Rheumatol 2013;9:311-18.
7. Grabiec AM, Krausz S, de Jager W, et al. Histone deacetylase inhibitors suppress inflammatory activation of rheumatoid arthritis patient synovial macrophages and tissue. J Immunol 2010;184:2718-28.
8. Grabiec AM, Korchynskyi O, Tak PP, et al. Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay. Ann Rheum Dis 2012;71:424-31.
9. Gillespie J, Savic S, Wong C, et al. Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone deacetylase 3-selective inhibitor reduces interleukin-6 production by peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Rheum 2012;64:418-22.
10. Filippakopoulos P, Knapp S. The bromodomain interaction module. FEBS Lett 2012;586:2692-704.
11. Prinjha RK, Witherington J, Lee K. Place your BETs: the therapeutic potential of bromodomains. Trends Pharmacol Sci 2012;33:146-53.
12. Sanchez R, Zhou MM. The role of human bromodomains in chromatin biology and gene transcription. Curr Opin Drug Discov Devel 2009;12:659-65.
13. Denis GV. Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation. Discov Med 2010;10:489-9.
14. Nicodeme E, Jeffrey KL, Schaefer U, et al. Suppression of inflammation by a synthetic histone mimic. Nature 2010;468:1119-23.
15. Belkina AC, Nikolajczyk BS, Denis GV. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J Immunol 2013;190:3670-8.
16. Bandukwala HS, Gagnon J, Togher S, et al. Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci USA 2012;109:14532-7.
17. Mele DA, Salmeron A, Ghosh S, et al. BET bromodomain inhibition suppresses TH17-mediated pathology. J Exp Med 2013;210:2181-90.
18. Kraan MC, Reece RJ, Smeets TJ, et al. Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: implications for pathogenesis and evaluation of treatment. Arthritis Rheum 2002;46:2034-8.
19. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
20. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039-49.
21. Ospelt C, Brentano F, Rengel Y, et al. Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis. Arthritis Rheum 2008;58:3684-92.
22. Trenkmann M, Brock M, Gay RE, et al. Tumor necrosis factor alpha-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-kappaB signaling. Arthritis Rheum 2013;65:916-27.
23. Ospelt C, Brentano F, Jungel A, et al. Expression, regulation, and signaling of the pattern-recognition receptor nucleotide-binding oligomerization domain 2 in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2009;60:355-63.
24. Mahdi H, Fisher BA, Kallberg H, et al. Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis. Nat Genet 2009;41:1319-24.
25. Justen HP, Grunewald E, Totzke G, et al. Differential gene expression in synovium of rheumatoid arthritis and osteoarthritis. Mol Cell Biol Res Commun 2000;3:165-72.
26. Knevel R, Klein K, Somers K, et al. Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis. Ann Rheum Dis 2014;73:2038-46.
27. Dawson MA, Prinjha RK, Dittmann A, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011;478:529-33.
28. Huang B, Yang XD, Zhou MM, et al. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 2009;29:1375-87.
29. Hamilton JA, Tak PP. The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis Rheum 2009;60:1210-21.
30. Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010;2:52ra72.
31. McInnes IB, Sieper J, Braun J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis 2014;73:349-56.
32. Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 2013;382:1705-13.