Abstract

Objective: To investigate anti-apoptogenic mechanism of transforming growth factor β1 (TGFβ1) towards synovial cells.

Methods: Isolated synovial cells, treated or not with TGFβ1, 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 (ΔΨm).

Results: Activation of caspase-9 and ΔΨm 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 TGFβ1 treated synovial cells. LLL-CHO, etoposide, and C2-ceramide also caused ΔΨm, 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, TGFβ1 significantly reduced apoptotic cell death of synovial cells induced by the above chemicals.

Conclusions: The protective effect of TGFβ1 for mitochondrial homoeostasis may be important in the anti-apoptogenic function of TGFβ1 for synovial cells.