title: Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli.
abstract: OBJECTIVE
  To investigate anti-apoptogenic mechanism of transforming growth factor beta1 (TGFbeta1) towards synovial cells.
  
  
  METHODS
  Isolated synovial cells, treated or not with TGFbeta1, were cultured in the presence or absence of anti-Fas IgM, proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or C2-ceramide. After cultivation, apoptosis of synovial cells was examined by the presence of hypodiploid DNA(+) cells, the presence of terminal deoxy (d)-UTP nick end labelling(+) cells (TUNEL(+) cells), activation of caspases, and disruption of mitochondrial transmembrane potential (DeltaPsim).
  
  
  RESULTS
  Activation of caspase-9 and DeltaPsim was found in anti-Fas IgM treated synovial cells. The increment of both hypodiploid DNA(+) cells and TUNEL(+) cells accompanied by the activation of caspase-8 and caspase-3 was also determined in anti-Fas IgM treated synovial cells. These hallmarks for apoptosis induced by anti-Fas IgM were significantly suppressed in TGFbeta1 treated synovial cells. LLL-CHO, etoposide, and C2-ceramide also caused DeltaPsim, the increment of both hypodiploid DNA(+) cells and TUNEL(+) cells, and the activation of both Leu-Glu-His-Asp ase (LEHDase; caspase-9 like activity) and Asp-Glu-Val-Asp ase (DEVDase; caspase-3 like activity) in synovial cells. As determined in anti-Fas IgM treatment, TGFbeta1 significantly reduced apoptotic cell death of synovial cells induced by the above chemicals.
  
  
  CONCLUSIONS
  The protective effect of TGFbeta1 for mitochondrial homoeostasis may be important in the anti-apoptogenic function of TGFbeta1 for synovial cells.
authors.affiliation: The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. atsushik@net.nagasaki-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Urayama
authors.forename: S
authors.initials: S
authors.lastname: Yamasaki
authors.forename: A
authors.initials: A
authors.lastname: Hida
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: M
authors.initials: M
authors.lastname: Kamachi
authors.forename: K
authors.initials: K
authors.lastname: Nakashima
authors.forename: F
authors.initials: F
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Ida
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: I
authors.initials: I
authors.lastname: Furuichi
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: T
authors.initials: T
authors.lastname: Origuchi
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology; D015153:Blotting, Western; D002478:Cells, Cultured; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D019014:fas Receptor / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019014:fas Receptor