Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis

被引:65
|
作者
Juengel, A.
Baresova, V.
Ospelt, C.
Simmen, B. R.
Michel, B. A.
Gay, R. E.
Gay, S.
Seemayer, C. A.
Neidhart, M.
机构
[1] Univ Zurich Hosp, Ctr Expt Rheumatol, Dept Rheumatol, CH-8091 Zurich, Switzerland
[2] Schulthess Clin, Zurich, Switzerland
[3] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland
关键词
D O I
10.1136/ard.2005.044065
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Histone acetylation/deacetylation has a critical role in the regulation of transcription by altering the chromatin structure. Objective: To analyse the effect of trichostatin A (TSA), a streptomyces metabolite which specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis of rheumatoid arthritis synovial fibroblasts (RASF). Methods: Apoptotic cells were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.5, 1, and 2 mmol/l) by flow cytometry using propidium iodide/annexin-V-FITC staining. Cell proliferation was assessed using the MTS proliferation test. Induction of the cell cycle inhibitor p21(Waf/Cip1) by TSA was analysed by western blot. Expression of the TRAIL receptor-2 (DR5) on the cell surface of RASF was analysed by flow cytometry. Levels of soluble TRAIL were measured in synovial fluid of patients with RA and osteoarthritis (OA) by ELISA. Results: Co-treatment of the cells with TSA and TRAIL induced cell death in a synergistic and dose dependent manner, whereas TRAIL and TSA alone had no effect or only a modest effect. RASF express DR5 (TRAIL receptor 2), but treatment of the cells with TSA for 24 hours did not change the expression level of DR5, as it is shown for cancer cells. TSA induced cell cycle arrest in RASF through up regulation of p21(Waf1/Cip1). Levels of soluble TRAIL were significantly higher in RA than in OA synovial fluids. Conclusion: Because TSA sensitises RASF for TRAIL-induced apoptosis, it is concluded that TSA discloses sensitive sites in the cascade of TRAIL signalling and may represent a new principle for the treatment of RA.
引用
收藏
页码:910 / 912
页数:3
相关论文
共 50 条
  • [1] Trichostatin a sensitizes rheumatoid arthritis synovial fibroblasts for TRAIL induced apoptosis.
    Juengel, A
    Baresova, V
    Simmen, BR
    Michel, BA
    Gay, RE
    Gay, S
    Seemayer, CA
    Neidhart, M
    [J]. ARTHRITIS AND RHEUMATISM, 2005, 52 (09): : S576 - S576
  • [2] Trichostatin-A sensitizes rheumatoid arthritis synovial fibroblasts for trail induced apoptosis
    Jüngel, A
    Baresova, V
    Simmen, BR
    Michel, BA
    Gay, RE
    Gay, S
    Seemayer, CA
    Neidhart, M
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2005, 64 : 453 - 453
  • [3] Regulating the sensitivity of synovial fibroblasts to trail-induced apoptosis
    Dharmapatni, AASSK
    Findlay, DM
    Smith, MD
    Evdokiou, A
    Chen, P
    Screaton, GR
    Xu, XN
    Holding, C
    Haynes, DR
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2005, 64 : 154 - 154
  • [4] Susceptibility of rheumatoid arthritis synovial fibroblasts to FasL- and TRAIL-induced apoptosis is cell cycle-dependent
    Noreen Pundt
    Marvin A Peters
    Christina Wunrau
    Simon Strietholt
    Carsten Fehrmann
    Katja Neugebauer
    Christine Seyfert
    Frans van Valen
    Thomas Pap
    Ingmar Meinecke
    [J]. Arthritis Research & Therapy, 11
  • [5] Susceptibility of rheumatoid arthritis synovial fibroblasts to FasL- and TRAIL-induced apoptosis is cell cycle-dependent
    Pundt, Noreen
    Peters, Marvin A.
    Wunrau, Christina
    Strietholt, Simon
    Fehrmann, Carsten
    Neugebauer, Katja
    Seyfert, Christine
    van Valen, Frans
    Pap, Thomas
    Meinecke, Ingmar
    [J]. ARTHRITIS RESEARCH & THERAPY, 2009, 11 (01)
  • [6] Downregulation of Mcl-1 by Ursolic Acid, a Pentacyclic Triterpenoid, Sensitizes Rheumatoid Arthritis Synovial Fibroblasts for TRAIL-Induced Apoptosis
    Zielinski, Carolyn
    Beamer, Maria
    Ahmed, Salahuddin
    [J]. ARTHRITIS AND RHEUMATISM, 2011, 63 (10): : S138 - S139
  • [7] Identification of genes regulating TRAIL-induced apoptosis in rheumatoid arthritis fibroblasts-like synoviocytes
    Audo, R.
    Hegglin, A.
    Severac, D.
    Dantec, C.
    Combe, B.
    Hahne, M.
    Morel, J.
    [J]. GENES AND IMMUNITY, 2015, 16 (07) : 462 - 469
  • [8] Identification of genes regulating TRAIL-induced apoptosis in rheumatoid arthritis fibroblasts-like synoviocytes
    R Audo
    A Hegglin
    D Severac
    C Dantec
    B Combe
    M Hahne
    J Morel
    [J]. Genes & Immunity, 2015, 16 : 462 - 469
  • [9] Signaling pathways involved in TRAIL-induced rheumatoid arthritis synovial fibroblast proliferation
    Morel, J.
    Audo, R.
    Combe, B.
    [J]. ARTHRITIS RESEARCH & THERAPY, 2005, 7 (Suppl 1) : S26 - S26
  • [10] Signaling pathways involved in TRAIL-induced rheumatoid arthritis synovial fibroblast proliferation
    J Morel
    R Audo
    B Combe
    [J]. Arthritis Research & Therapy, 7