[en] OBJECTIVE: To investigate the effects of endogenously produced nitric oxide (NO) on interleukin 6 (IL-6), IL-8, prostaglandin E2 (PGE2), and proteoglycan production by human chondrocytes. METHODS: Human articular chondrocytes were isolated from their extracellular matrix by triple successive enzymatic digestion of the cartilage and cultured 48 h in a well defined culture medium. IL-6 and IL-8 were directly assayed into culture media by specific enzyme amplified sensitivity immunoassays. Proteoglycans and PGE2 were quantified by specific radioimmunoassays. Cell culture media were assayed for NO2 using a spectrophotometric assay based upon the Griess reaction. RESULTS: Unstimulated chondrocytes produced low levels of NO, IL-6, IL-8, and PGE2. Production was significantly stimulated by IL-1beta and lipopolysaccharide (LPS). As well, proteoglycan synthesis was profoundly inhibited by IL-1beta and LPS. Inhibition of NO synthesis with the competitive inhibitor NG-monomethyl-L-arginine (L-NMMA) led to enhancement of IL-6, IL-8, and PGE2 production stimulated by either IL-1beta alone or in combination with LPS, whereas the inhibition of proteoglycan production by IL-1beta was not modified by L-NMMA. CONCLUSION: LPS and IL-1beta stimulated IL-6, IL-8, and PGE2 production are downregulated by endogenously produced NO, which could limit the inflammatory reaction occurring in arthritis.
Disciplines :
Rheumatology
Author, co-author :
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Zheng, S. X.
Dupont, Ginette ; Université de Liège - ULiège > Centres généraux > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Labasse, A. H.
Crielaard, Jean-Michel ; Université de Liège - ULiège > Département des sciences de la motricité > Evaluation et entraînement des aptitudes physiques
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
Nitric Oxide Downregulates Interleukin 1β (IL-1β) Stimulated IL-6, IL-8, and Prostaglandin E2 Production by Human Chondrocytes
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