The Journal of Immunology, Vol 147, Issue 4 1238-1246, Copyright © 1991 by American Association of Immunologists

ARTICLES

Human articular cartilage and chondrocytes produce hemopoietic colony- stimulating factors in culture in response to IL-1

IK Campbell, U Novak, J Cebon, JE Layton and JA Hamilton
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Victoria, Australia.

The hemopoietic CSF, granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), are cytokines that mediate the clonal proliferation and differentiation of progenitor cells into mature macrophages and/or granulocytes. We have employed an all-human cell culture system, specific ELISA for GM-CSF and G-CSF, and Northern analysis to investigate whether chondrocytes are a potential source of CSF in rheumatoid disease. We report that human rIL-1 stimulated in a dose-dependent manner the production of GM-CSF and G-CSF by human articular cartilage and chondrocyte monolayers in organ and cell culture, respectively. Increased levels of the CSF Ag were detected after 2 to 8 h stimulation with IL-1, and the optimum dose of IL-1 was 10 to 100 U/ml (0.06 to 0.6 nM IL-1 alpha; 0.02 to 0.2 nM IL-1 beta); neither CSF was detectable in nonstimulated cultures nor in IL-1- stimulated cultures treated with actinomycin D or cycloheximide, indicating the requirement for de novo RNA and protein synthesis. The IL-1-mediated increase in GM-CSF could also be inhibited by the corticosteroid, dexamethasone, but not by the cyclo-oxygenase inhibitor, indomethacin. Although having little effect when tested alone, TNF-alpha and lymphotoxin (TNF-beta) could synergize with IL-1 for the production of GM-CSF. Basic fibroblast growth factor, platelet- derived growth factor, and IFN-alpha and IFN-gamma each had no effect on GM-CSF levels. Results obtained by Northern analysis of chondrocyte total RNA reflected those found for the CSF Ag, namely that CSF mRNA levels were elevated in response to IL-1, but not TNF, and that there was synergy between these two cytokines. We propose that chondrocyte CSF production in response to IL-1, and the concurrent destruction of cartilage by IL-1, could provide a mechanism for the chronic nature of rheumatoid disease.

This article has been cited by other articles:

				K. E. Lawlor, I. K. Campbell, D. Metcalf, K. O'Donnell, A. van Nieuwenhuijze, A. W. Roberts, and I. P. Wicks Critical role for granulocyte colony-stimulating factor in inflammatory arthritis PNAS, August 3, 2004; 101(31): 11398 - 11403. [Abstract] [Full Text] [PDF]

				I. K. Campbell, M. J. Rich, R. J. Bischof, and J. A. Hamilton The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF J. Leukoc. Biol., July 1, 2000; 68(1): 144 - 150. [Abstract] [Full Text]

				J. E. Layton, G. Shimamoto, T. Osslund, A. Hammacher, D. K. Smith, H. R. Treutlein, and T. Boone Interaction of Granulocyte Colony-stimulating Factor (G-CSF) with Its Receptor. EVIDENCE THAT Glu19 of G-CSF INTERACTS WITH Arg288 OF THE RECEPTOR J. Biol. Chem., June 18, 1999; 274(25): 17445 - 17451. [Abstract] [Full Text] [PDF]

				I. K. Campbell, M. J. Rich, R. J. Bischof, A. R. Dunn, D. Grail, and J. A. Hamilton Protection from Collagen-Induced Arthritis in Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice J. Immunol., October 1, 1998; 161(7): 3639 - 3644. [Abstract] [Full Text] [PDF]

				I. K Campbell, A. Bendele, D. A Smith, and J. A Hamilton Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice Ann Rheum Dis, June 1, 1997; 56(6): 364 - 368. [Abstract] [Full Text]