Visit our Expo - Redox and Inflammation signaling 2012

Session XVI : Chemopreventive agents Poster XVI, 11
Resveratrol Inhibits IL-1#-Induced Stimulation of Caspase 3 and Apoptosis in Human
Articular Chondrocytes in vitro
Shakibaei M1, John T2, Seifarth C1, Mobasheri A3
1Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-
University Munich, Pettenkoferstrasse 11, 80336 Munich; 2Charité Medicine University
Berlin, Campus Benjamin Franklin, Department for Trauma Surgery, Berlin,
Germany; 3Connective Tissue and Molecular Pathogenesis Research Groups, Faculty of
Veterinary Science, University of Liverpool, United Kingdom.
Resveratrol (trans-3,4´-trihydroxystilbene) is a polyphenolic phytoalexin that is present in
various fruits, in the skin of red grapes, peanuts and root extracts. Recent studies have shown
that resveratrol exhibits potent antioxidant properties and is able to exert anti-inflammatory
and anti-catabolic properties in several cell types. The pro-inflammatory cytokine interleukin
1 # (IL-1#) plays a pivotal role in the pathogenesis of osteoarthritis (OA) in humans and
animals. In this study we investigated whether resveratrol is able to block the proinflammatory
effects of IL-1#, specifically the activation of caspase 3 and subsequent
induction of apoptosis in human articular chondrocytes.
Cultures of human articular chondrocytes were pre-stimulated with 10 ng/ml IL-1# for 1, 12
and 24 h before being co-treated with IL-1# and 100 µM/ml resveratrol or 50µM the caspase
inhibitor Z-DEVD-FMK for 1, 12 and 24 h respectively in vitro.
Resveratrol significantly increased the IL-1#-induced inhibition the attenuated expression of
cartilage specific collagen type II and signal transduction receptor integrin #1 in a time
dependent manner. Incubation of chondrocytes with IL-1# resulted in activation of the
cysteine protease caspase 3, PARP cleavage and apoptotic cell death. In this report we present
evidence from ultrastructural studies that mitochondria play a major role in IL-1#-induced
apoptosis. The treatment of human chondrocytes with IL-1# induced mitochondrial swelling
in a time-dependent manner. These changes were observed as early as 1 hour after treatment
of cells with IL-1#. These effects (activation of caspase 3, cleavage of PARP and
mitochondrial changes) were abolished through the co-treatment with resveratrol.
Furthermore, co-treatment of the IL-1#–stimulated cells with the caspase inhibitor Z-DEVD-
FMK blocked apoptosis as shown by electron microscopy and Western blotting, suggesting
that this process is a caspase-dependent pathway.
In summary, our results confirm that resveratrol is an effective in vitro inhibitor of caspase 3
and apoptosis in human chondrocytes. These findings suggest that this dietary polyphenolic
compound may have future applications in the nutraceutical based therapy of human and
animal OA.
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