Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. II: Glycosaminoglycan synthesis.
The effect of Etodolac on glycosaminoglycan (GAG) synthesis by human synovial cells and rabbit articular chondrocytes in culture was studied at doses ranging from 0.01 to 10 micrograms/ml. In chondrocyte cultures, short-term exposure to Etodolac decreased the total amount of GAGs (mainly chondroitin sulfate) affecting essentially the cell layer-associated fraction. When cells were incubated with Interleukin-1 (IL-1), Etodolac still exerted its inhibiting effect on GAG synthesis. Long-term exposure of chondrocytes to Etodolac caused a diminution of the total GAG synthesis for the highest concentration studied (1 micrograms/ml). IL-1 alone or in combination with Etodolac decreased the synthesis of GAGs suggesting that pretreatment with Etodolac cannot prevent the action of IL-1. In synoviocyte cultures, the drug caused an inhibition of the GAG biosynthesis (mainly hyaluronic acid). In presence of IL-1, Etodolac at the highest concentration partially diminished the stimulatory effect of IL-1. A 8-day exposure of the cells to Etodolac led to a decrease of GAG synthesis. In the same experiment, IL-1 alone caused a slight increase of GAG production that was not abolished by Etodolac treatment.
Redini
F
F
Laboratoire de Biochimie du Tissu Conjonctif, C.H.U. Côte de Nacre, Caen, France.
Mauviel
A
A
Loyau
G
G
Pujol
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D017308:Etodolac; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007210:Indoleacetic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D011817:Rabbits; D012216:Rheumatic Diseases / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007210:Indoleacetic Acids; D007375:Interleukin-1; D017308:Etodolac