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Article Dans Une Revue Biorheology Année : 2002

Nitric oxide (NO) and cartilage metabolism: NO effects are modulated by superoxide in response to IL-1

Résumé

Nitric oxide (NO) is thought to mediate most effects of interleukin-1 (IL-1) on cartilage. In vitro evidence includes the decreased synthesis of extracellular matrix components, the abnormal cell renewal, the decreased production of IL-1 receptor antagonist, the induction of apoptosis and the enhanced sensitivity of chondrocytes to oxidative stress. Studies in NOS2(-/-) mice or administration of NO synthase inhibitors in animal models of joint disorders have confirmed its potent pathophysiological role in cartilage. Using L-NMMA (1 mM), as a NO synthase inhibitor, and CuDips (10 microM), as a SOD mimetic, we provide evidence that the inhibitory potency of IL-1beta on proteoglycan synthesis and its stimulating effect on COX-2 activity depend both on NO and O2-* production. Peroxynitrite formation is further demonstrated by the occurrence of 3-nitrotyrosines in chondrocytes stimulated in vitro with 2.5 ng/ml IL-1 and in femoral condyles of rats injected locally with 1 microg IL-1. Preliminary data suggest that such contribution of reactive oxygen species is not shared in common by IL-17, another NO-producing cytokine. We conclude that superoxide is a key modulator of NO-mediated effects in chondrocyte stimulated with IL-1 and that a combined therapy with NO synthase inhibitors and antioxidants may be promising for a full cartilage protection.

Dates et versions

hal-00466563 , version 1 (24-03-2010)

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Jean-Yves Jouzeau, Sandrine Pacquelet, Christelle Boileau, Emmanuelle Nédélec, Nathalie Presle, et al.. Nitric oxide (NO) and cartilage metabolism: NO effects are modulated by superoxide in response to IL-1. Biorheology, 2002, 39 (1-2), pp.201-14. ⟨hal-00466563⟩
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