Effect of interleukin 1 and leukaemia inhibitory factor on chondrocyte metabolism in articular cartilage from normal and interleukin-6-deficient mice: role of nitric oxide and IL-6 in the suppression of proteoglycan synthesis.
We studied the role of IL-6 and nitric oxide (NO) in IL-1 and leukaemia inhibitory factor (LIF) induced suppression of proteoglycan synthesis. Cartilage explants of patellae and femoral heads were incubated with IL-1 or LIF. Conditioned media were analysed for IL-6 activity (B9-assay) and NO content (Griess). Proteoglycan synthesis was assessed using [35S]sulfate incorporation. IL-1 dose dependently induced IL-6 synthesis and neutralizing IL-6 with antibodies did not reduce proteoglycan synthesis suppression, neither in explants nor in isolated chondrocytes. IL-6 independence was confirmed using cartilage from IL-6 deficient mice. IL-1 significantly increased NO release in normal and IL-6 deficient chondrocytes and addition of the NO synthase inhibitor, N(G)-monomethyl-L-arginine markedly alleviated proteoglycan synthesis suppression. LIF also induced proteoglycan synthesis suppression in cartilage from normal and IL-6 deficient mice, but the suppression was neither accompanied by nor dependent on NO release. Furthermore, proteoglycan synthesis suppression during experimental arthritis was similar in both normal and IL-6 deficient mice. We concluded that IL-6 is not a necessary cofactor in IL-1 and LIF induced suppression of proteoglycan synthesis. Furthermore, only the IL-1 induced suppression was mediated by NO, suggesting that inhibition of proteoglycan synthesis may occur through different pathways.
Van de Loo
F A
FA
Department of Rheumatology, University Hospital Nijmegen, The Netherlands. A.vandeloo@reuma.azn.nl
Arntz
O J
OJ
Van den Berg
W B
WB
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011509:Proteoglycans; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I