Regulation of interleukin 1 receptors in human articular chondrocytes.
Interleukin 1 (IL-1) exerts pronounced effects on articular cartilage by increasing matrix molecule turnover and metalloprotease synthesis. These effects are believed to be mediated through a high affinity cell surface receptor (IL-1R) present on chondrocytes. Normal human chondrocytes express about 3,000-5,000 sites/cell. The downregulation of IL-1R could potentially reduce the biological effectiveness of IL-1 and as a result influence inflammatory conditions. Agents which modulate the number of IL-1R were investigated. Cytokines, such as IL-1 alpha (1 ng/ml) and IL-1 beta (1 ng/ml), were found to reduce the chondrocyte IL-1R level by about 78% versus the control. Other cytokines tested, IL-2 (20 ng/ml) and tumor necrosis factor-alpha (1 ng/ml), also reduced IL-1R levels but to a lesser extent; 52 and 69% inhibition were recorded, respectively. The growth factor bFGF (50 ng/ml) induced a 48% reduction versus the basal level, and a therapeutic dosage of indomethacin (1.5 micrograms/ml) elicited only a slight reduction (10%). Hydrocortisone had a variable effect on the IL-1R level.
McCollum
R
R
Rheumatic Diseases Unit Research Laboratory, Notre-Dame Hospital Research Center, Montreal, PQ, Canada.
Martel-Pelletier
J
J
DiBattista
J
J
Pelletier
J P
JP
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology*; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006133:Growth Substances; D007376:Interleukin-2; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin