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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.

journal_name

Ann Rheum Dis

journal_title

Annals of the rheumatic diseases

authors

Kawakami A,Urayama S,Yamasaki S,Hida A,Miyashita T,Kamachi M,Nakashima K,Tanaka F,Ida H,Kawabe Y,Aoyagi T,Furuichi I,Migita K,Origuchi T,Eguchi K

doi

10.1136/ard.2003.014159

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

95-7

issue

eissn

0003-4967

issn

1468-2060

journal_volume

pub_type

杂志文章

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Anti-apoptogenic function of TGFbeta1 for human synovial cells: TGFbeta1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli.