title: IL-17-mediated Bcl-2 expression regulates survival of fibroblast-like synoviocytes in rheumatoid arthritis through STAT3 activation.
abstract: BACKGROUND
  Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades adjacent cartilage and bone in rheumatoid arthritis (RA). The study was undertaken to determine the effect of interleukin-17 (IL-17) on the survival and/or proliferation of FLSs from RA patients and to investigate whether signal tranducer and activator of transcription 3 (STAT3) is implicated in this process.
  
  
  METHODS
  Bcl-2 and Bax expression in FLSs was determined using the real-time PCR and western blot analysis. The expression of Bcl-2 and phosphoSTAT3 in synovial tissues was investigated by confocal microscope. Apoptosis of FLSs was detected by Annexin V/propidium iodide staining and/or phase contrast microscopy. The proliferation of FLSs was determined by CCK-8 ELISA assay.
  
  
  RESULTS
  The pro-apoptotic Bax is decreased and anti-apoptotic Bcl-2 is increased in FLSs from RA patients compared with those from patients with osteoarthritis (OA). IL-17 upregulated the expression of Bcl-2 in FLSs from RA patients, but not in FLSs from OA patients. STAT3 was found to mediate IL-17-induced Bcl-2 upregulation in FLSs from RA patients. Additionally, IL-17 promoted the survival and proliferation of FLSs from RA patients. Most importantly, treatment with STAT3 inhibitor reversed the protective effect of IL-17 on FLSs apoptosis induced by sodium nitroprusside (SNP).
  
  
  CONCLUSIONS
  Our data demonstrate that STAT3 is critical in IL-17-induced survival of FLS from RA patients. Therefore, therapeutic strategies that target the IL-17/STAT3 pathway might be strong candidates for RA treatment modalities.
authors: Seon-Yeong
authors: SY
authors: Lee
authors: Seung-Ki
authors: SK
authors: Kwok
authors: Hye-Jin
authors: HJ
authors: Son
authors: Jun-Geol
authors: JG
authors: Ryu
authors: Eun-Kyung
authors: EK
authors: Kim
authors: Hye-Jwa
authors: HJ
authors: Oh
authors: Mi-La
authors: ML
authors: Cho
authors: Ji Hyeon
authors: JH
authors: Ju
authors: Sung-Hwan
authors: SH
authors: Park
authors: Ho-Youn
authors: HY
authors: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human