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. |
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| Authors: | P A Guerne A Desgeorges J M Jaspar B Relic R Peter P Hoffmeyer J M Dayer |
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| Institution: | 1. Division of Rheumatology, Hôpital Cantonal Universitaire, 26 av. Beau-Séjour, 1211 Geneva 14, Switzerland;2. Biosource Europe S.A., Nivelle, Belgium;3. Division of Orthopaedic Surgery, Hôpital Cantonal Universitaire, 1211 Geneva 14, Switzerland;4. Division of Immunology and Allergy, Hôpital Cantonal Universitaire, 1211 Geneva 14, Switzerland;1. China Medical University, Shenyang 110013, China;2. The Fourth Affiliated Hospital of China Medical University, Shenyang 110122, China;3. The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China;1. Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai 599-8531, Japan;2. Tokyo Midtown Medical Center, Akasaka 9-7-1, Minato-ku, Tokyo 107-6243, Japan;1. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA02215, United States;2. Boston University Medical Center, United States;1. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2. Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;3. Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea |
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| 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. |
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