Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA).
This study examines the role of interleukin-6 (IL-6) in connective tissue metabolism. Effects of different preparations of IL-6 on production of collagenase and tissue inhibitor of metalloproteinases-1/erythroid potentiating activity production are studied in human fibroblasts, synoviocytes, and articular chondrocytes. In contrast to interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha), IL-6 does not stimulate the production of collagenase, nor does it modulate the stimulatory effects of IL-1 beta and TNF alpha on the production of this proteinase. Furthermore, IL-6 has no detectable effect on prostaglandin E2 production, an additional proinflammatory response induced by IL-1 beta and TNF alpha. IL-6, however, is identified as a potent inducer of de novo synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity in all types of connective tissue cells examined. These results define new biological activities of IL-6 and provide further insight into the regulation of connective tissues by cytokines.
Lotz
M
M
Department of Medicine, University of California, San Diego, La Jolla 92093.
Guerne
P A
PA
D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D003012:Microbial Collagenase / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases; D003012:Microbial Collagenase; D015232:Dinoprostone