Effects of IL-6 and its soluble receptor on proteoglycan synthesis and NO release by human articular chondrocytes: comparison with IL-1. Modulation by dexamethasone

Article Article scientifique Article Effects of IL-6 and its soluble receptor on proteoglycan synthesis and NO release by human articular chondrocytes: comparison with IL-1. Modulation by dexamethasone eng 1999 author Guerne Pierre-André 29463 author Desgeorges Alain 29932 author Jaspar JM author Relic Biserka 24349 author Peter Robin 62978 author Hoffmeyer Pierre 29797 author Dayer Jean-Michel 25468 253-260 10.1016/S0945-053X(99)00021-9 10429944 0945-053X Contradictory results have been reported on the effects and role of IL-6 on proteoglycan (PG) synthesis. Having shown recently that in vitro IL-6 depends on the presence of soluble IL-6 receptor alpha (sIL-6Ralpha) to fully exert its effects on chondrocytes, we conducted the present study to analyse the effects of IL-6 on PG synthesis by human articular chondrocytes in the presence of sIL-6Ralpha. PG synthesis was quantified by specific ELISA using a monoclonal antibody (MAB) raised against the keratan sulphate region of PG as a capture antibody, and a MAB to the acid binding region as a detector. It proved specific for PG from primary (differentiated) chondrocytes. In the absence of sIL-6Ralpha, IL-6 had a slight inhibitory effect on PG synthesis by articular chondrocytes. sIL-6Ralpha alone also had slight but consistent inhibitory effects. When adding sIL-6Ralpha at concentrations of 50 ng/ml corresponding to levels found in synovial fluid, the effects of IL-6 increased consistently. However, even at optimal concentrations (30-100 ng/ml of IL-6sR per 100 ng/ml of IL-6), maximal inhibition (48%) did not equal the degree of inhibition achieved by IL-1 at 1 ng/ml (66%). Similar effects, although slightly weaker, were observed on osteoarthritic cells. Dexamethasone, over a wide range of concentrations, markedly enhanced proteoglycan synthesis and completely reversed the downregulatory effects of IL-1 and IL-6 + sIL-6Ralpha. The effects of IL-1 were partially inhibited by an anti-IL-6 antibody. Finally, unlike IL-1, IL-6 + sIL-6Ralpha only weakly stimulated nitric oxide (NO) synthesis. In conclusion, sIL-6Ralpha potentiates the inhibitory effect of IL-6 on PG synthesis by articular chondrocytes, but the overall effect of IL-6 + IL-6sR is moderate compared to the effects of IL-1. Animals Cartilage, Articular/cytology/metabolism Chondrocytes/drug effects/metabolism Dexamethasone/metabolism/pharmacology Glucocorticoids/metabolism/pharmacology Humans Interleukin-1/metabolism/pharmacology Interleukin-6/metabolism/pharmacology Mice Nitric Oxide/metabolism Osteoarthritis Proteoglycans/biosynthesis Receptors, Interleukin-6/metabolism Tumor Cells, Cultured Dewey 616 Dewey 617 56 Département de médecine 221 57 Département de chirurgie 222 false 74 Chirurgie orthopédique et traumatologique 98 75 Traumatologie ostéoarticulaire 99 Matrix biology 18 3 4a94283d-a8ff-4883-8292-458171f4ab28 Article (Published version) Restricted 1-s2.0-S0945053X99000219-main.pdf 197010 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Effects of IL-6 and its soluble receptor on proteoglycan synthesis and NO release by human articular chondrocytes: comparison with IL-1. Modulation by dexamethasone	Matrix biology			1999	592	0

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Desgeorges, Alain