Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro

The inflammatory process plays a pivotal role during the pathogenesis of osteoarthritis, dominated by catabolic processes initiated by pro-inflammatory cytokines such as IL-1 beta. Resveratrol, a natural phytoalexin occurring in various fruits has previously been shown to exhibit anti-inflammatory properties in several cell types. We investigated, whether resveratrol may be a useful blocker of pro-inflammatory cytokine signalling pathways in arthritis. We first examined the effects of resveratrol on the proliferation and production of ILAP in primary human articular chondrocytes treated with IL-1 beta in vitro. Resveratrol. reversed significantly IL-I beta-reduced cell proliferation and blocked IL-1 beta-stimulated cell membrane bound- and mature IL-1 beta synthesis in chondrocytes. Furthermore, resveratrol was able to inhibit the IL-1 beta-induced degradation of mitochondria and apoptosis in chondrocytes in a time-dependent manner. Because caspase inhibitor Z-DEVD-FMK abolished the IL-1 beta-induced apoptosis in chondrocytes, we examined the effect of resveratrol on the caspase pathway and found that resveratrol. blocked the cysteine protease caspase-3 and subsequent cleavage of the DNA repair enzyme PARP. Additionally, resveratrol reversed the IL-1 beta induced up-regulation of reactive oxygen species (ROS) in chondrocytes. Finally, we show that resveratrol induced ubiquitin-independent degradation of tumor suppressor gene protein p53 and inhibited p53-induced apoptosis in chondrocytes in a dose-dependent manner. our results indicate that resveratrol seems to be an effective in vitro anti-inflammatory agent and has a chondroprotective capacity through suppression of (1) IL-1 beta- (2) ROS- and (3) tumor suppressor protein p53-production. Further studies should be undertaken to define a possible implication of resveratrol in osteoarthritis therapy and cartilage tissue engineering. (c) 2007 Elsevier Inc. All rights reserved.