Effect of cytokines and anti-arthritic drugs on glycosaminoglycan synthesis by bovine articular chondrocytes.
The effect of cytokines (interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha) and several anti-arthritic drugs on glycosaminoglycan synthesis and secretion into medium by bovine articular chondrocytes was examined. Sulfated glycosaminoglycans (S-GAG) were measured by a modified 1,9-dimethylmethylene blue (DMB) dye binding assay. Hyaluronate (HA) was measured by an inhibition ELISA based on specific binding to a proteoglycan. All three cytokines caused a dose-dependent decrease in S-GAG production and a dose-dependent increase in HA production. Non-steroidal anti-inflammatory drugs (NSAIDs, indomethacin, naproxen, and piroxicam, 1 microM) could not reverse the effect of IL-1 alpha on inhibiting S-GAG and stimulating HA synthesis. The anti-inflammatory steroid (dexamethasone, 1 microM) depressed HA synthesis by 50-70% in the absence or presence of IL-1 alpha. Dexamethasone depressed S-GAG synthesis by 20-30% in the absence or presence of IL-1 alpha. Therefore, none of the tested anti-rheumatic drugs reversed the cytokine mediated changes in glycosaminoglycan synthesis by bovine chondrocytes.
Kolibas
L M
LM
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
Goldberg
R L
RL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006632:Histamine / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D006820:Hyaluronic Acid