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Scientific article
English

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

Published inMatrix biology, vol. 18, no. 3, p. 253-260
Publication date1999
Abstract

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.

Keywords
  • 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
Citation (ISO format)
GUERNE, Pierre-André et al. 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. In: Matrix biology, 1999, vol. 18, n° 3, p. 253–260. doi: 10.1016/S0945-053X(99)00021-9
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Article (Published version)
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ISSN of the journal0945-053X
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