Induction of interleukin-1 receptors on chondrocytes by fibroblast growth factor: a possible mechanism for modulation of interleukin-1 activity.
Interleukin-1 is a polypeptide factor with profound effects on several cell types, such as chondrocytes, fibroblasts, and T-cells. The ability of interleukin-1 to induce the synthesis of matrix-degradative enzymes, as well as prostaglandin E2, suggests a pivotal role for this mediator in chronic inflammation. Previous studies have shown that the effect of human monocyte interleukin-1 on the synthesis of collagenase and neutral proteases by chondrocytes was enhanced by basic fibroblast growth factor. Using recombinant human interleukin-1B, we have examined whether the potentiation of interleukin-1 effects by fibroblast growth factor is related to changes in the number or affinity of interleukin-1 receptors. Our studies confirm that rabbit articular chondrocytes in culture contain a single class of high-affinity receptors for interleukin-1 with a Ka of 0.9-1.1 x 10(-13) M-1. While the untreated chondrocytes contain approximately 1,620 receptors per cell, fibroblast growth factor-treated cells exhibit a higher number of receptors (approximately 2,960 per cell) with no apparent change in the affinity. The increase in receptor number can be abolished by inhibitors of lysosomal function, indicating a requirement for intracellular processing of the fibroblast growth factor. Our results suggest that the potentiation of interleukin-1 catabolic effects by fibroblast growth factor may be related to its ability to induce additional interleukin-1 receptors on the chondrocyte cell surface.
Chandrasekhar
S
S
Department of Connective Tissue and Monoclonal Antibody Research, Lilly Research Laboratories, Indianapolis, Indiana 46285.
Harvey
A K
AK
D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008666:Metalloendopeptidases / Q000378:metabolism; D003012:Microbial Collagenase / Q000096:biosynthesis; D011817:Rabbits; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D017472:Receptors, Interleukin-1
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D005346:Fibroblast Growth Factors; D008666:Metalloendopeptidases; D003012:Microbial Collagenase