Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation.
It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase and that such degradation is regulated by metalloproteinase inhibitors. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1 beta-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.
Department of Clinical Immunology, Kyushu University, Beppu, Japan.
M
M
Shingu
T
T
Isayama
C
C
Yasutake
T
T
Naono
M
M
Nobunaga
K
K
Tomari
K
K
Horie
Y
Y
Goto
D001172:Arthritis, Rheumatoid / Q000473:pathology; D002356:Cartilage / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D013481:Superoxides / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D016166:Free Radical Scavengers; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D004492:Edetic Acid; D017364:Collagenases; D007213:Indomethacin