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 - PubMed (original) (raw)

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

F A Van de Loo et al. Cytokine. 1997 Jul.

Free article

Abstract

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.

PubMed Disclaimer

Cited by

Breaking old paradigms: Th17 cells in autoimmune arthritis.
Peck A, Mellins ED. Peck A, et al. Clin Immunol. 2009 Sep;132(3):295-304. doi: 10.1016/j.clim.2009.03.522. Epub 2009 Apr 28. Clin Immunol. 2009. PMID: 19403336 Free PMC article. Review.
Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models.
van de Loo FA, Bennink MB, Arntz OJ, Smeets RL, Lubberts E, Joosten LA, van Lent PL, Coenen-de Roo CJ, Cuzzocrea S, Segal BH, Holland SM, van den Berg WB. van de Loo FA, et al. Am J Pathol. 2003 Oct;163(4):1525-37. doi: 10.1016/S0002-9440(10)63509-2. Am J Pathol. 2003. PMID: 14507659 Free PMC article.
Loss of transforming growth factor counteraction on interleukin 1 mediated effects in cartilage of old mice.
Scharstuhl A, van Beuningen HM, Vitters EL, van der Kraan PM, van den Berg WB. Scharstuhl A, et al. Ann Rheum Dis. 2002 Dec;61(12):1095-8. doi: 10.1136/ard.61.12.1095. Ann Rheum Dis. 2002. PMID: 12429542 Free PMC article.
Joint inflammation and cartilage destruction may occur uncoupled.
van den Berg WB. van den Berg WB. Springer Semin Immunopathol. 1998;20(1-2):149-64. doi: 10.1007/BF00832004. Springer Semin Immunopathol. 1998. PMID: 9836374 Review.
Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1beta.
Vincenti MP, Brinckerhoff CE. Vincenti MP, et al. Arthritis Res. 2001;3(6):381-8. doi: 10.1186/ar331. Epub 2001 Sep 18. Arthritis Res. 2001. PMID: 11714393 Free PMC article.

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 - PubMed (original) (raw)