Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis
- 25 July 2003
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 197 (3) , 379-387
- https://doi.org/10.1002/jcp.10372
Abstract
This study addresses mechanisms by which interleukin‐1β (IL‐1β) regulates human chondrocyte apoptosis induced by a combination of the anti‐CD95 antibody CH‐11 and the proteasome inhibitor (PSI). The effect of IL‐1β on apoptosis varied among tissue samples. IL‐1β either enhanced (16/22 samples) or inhibited (6/22 samples) DNA fragmentation and caspase‐3 processing. The protective effect of IL‐1β was abrogated by the nitric oxide (NO) synthesis inhibitor N‐monomethyl‐l‐arginine (L‐NMMA) while apoptosis stimulation was not affected. The NO‐donors sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl penicillamine (SNAP) blocked DNA fragmentation, and this was associated with partial inhibition of caspase‐3 processing. Pyrrolidine dithiocarbamate (PDTC), a scavenger of reactive oxygen species (ROS) blocked apoptosis induction by CH‐11/PSI as well as the enhancement by IL‐1β. The pro‐apoptotic effects of IL‐1β were also abrogated by the p38 inhibitor SB 202190. In conclusion, IL‐1β augments CH‐11/PSI induced apoptosis in the majority of chondrocyte samples. The pro‐apoptotic effect of IL‐1β is not dependent on NO. In contrast, the anti‐apoptotic effect of IL‐1β observed in a minority of samples is partially NO‐dependent. J. Cell. Physiol. 197: 379–387, 2003Keywords
Funding Information
- the National Institute of Health (AR42438, AG07996)
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