Interleukin-1beta and Interleukin-6 Disturb the Antioxidant Enzyme System in Bovine Chondrocytes: A Possible Explanation for Oxidative Stress Generation
[en] OBJECTIVE: Beside matrix metalloproteinases, reactive oxygen species (ROS) are the main biochemical factors of cartilage degradation. To prevent ROS toxicity, chondrocytes possess a well-coordinated enzymatic antioxidant system formed principally by superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPX). This work was designed to assess the effects of interleukin (IL)-1beta and IL-6 on the enzymatic activity and gene expression of SODs, CAT and GPX in bovine chondrocytes. METHODS: Bovine chondrocytes were cultured in monolayer for 4-96h in the absence or in the presence of IL-1beta (0.018-1.8ng/ml) or IL-6 (10-100ng/ml). To study signal transduction pathway, inhibitors of mitogen-activated protein kinases (MAPK) (PD98059, SB203580 and SP600125) (5-20muM) and nuclear factor (NF)-kappaB inhibitors [BAY11-7082 (1-10muM) and MG132 (0.1-10muM)] were used. SODs, CAT and GPX enzymatic activities were evaluated in cellular extract by using colorimetric enzymatic assays. Mn SODs, Cu/Zn SOD, extracellular SOD (EC SOD), CAT and GPX gene expressions were quantified by real-time and quantitative polymerase chain reaction (PCR). RESULTS: Mn SOD and GPX activities were dose and time-dependently increased by IL-1beta. In parallel, IL-1beta markedly enhanced Mn SOD and GPX gene expressions, but decreased Cu/Zn SOD, EC SOD and CAT gene expressions. Induction of SOD enzymatic activity and Mn SOD mRNA expression were inhibited by NF-kappaB inhibitors but not by MAPK inhibitors. IL-6 effects were similar but weaker than those of IL-1beta. CONCLUSIONS: In conclusion, IL-1beta, and to a lesser extend IL-6, dysregulates enzymatic antioxidant defenses in chondrocyte. These changes could lead to a transient accumulation of H(2)O(2) in mitochondria, and consequently to mitochondria damage. These changes contribute to explain the mitochondrial dysfunction observed in osteoarthritis chondrocytes.
Disciplines :
Rheumatology
Author, co-author :
Mathy, Marianne ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Sanchez, Christelle ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Deby, Ginette ; Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Crielaard, Jean-Michel ; Université de Liège - ULiège > Département des sciences de la motricité > Evaluation et entraînement des aptitudes physiques
Henrotin, Yves ; Université de Liège - ULiège > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Language :
English
Title :
Interleukin-1beta and Interleukin-6 Disturb the Antioxidant Enzyme System in Bovine Chondrocytes: A Possible Explanation for Oxidative Stress Generation
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