Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis.
Cultures of human rheumatoid synovial cells and rabbit articular chondrocytes were exposed to various concentrations of Etodolac (from 0.01 to 10 micrograms/ml) in presence or absence of 500 pg/ml (5 U/ml) human recombinant Interleukin-1 beta (IL-1 beta). Incubation of chondrocytes with Etodolac for 24 h did not alter collagen biosynthesis. In contrast, 1 micrograms/ml Etodolac caused a 20% increase of collagen production in synoviocytes. Addition of Etodolac in combination with IL-1 could partially suppress the inhibitory effect exerted by the cytokine on both cell types. Four-day exposure of chondrocytes to 0.1 and 1 micrograms/ml Etodolac led to an increased accumulation of collagen in the cell layer compartment. However, this treatment could not prevent the inhibitory effect of IL-1 on this collagen fraction. Treatment of synoviocytes for eight days with the same concentrations of Etodolac did not modify their collagen production but suppressed totally the inhibitory effect of IL-1. These data show that Etodolac is able to augment chondrocyte metabolism during a long term treatment. Moreover, under certain conditions, this drug can reduce or even suppress the IL-1-induced inhibition of collagen biosynthesis, a process that may take a part in the connective tissue alterations associated with osteoarticular diseases such as rheumatoid arthritis and osteoarthritis.
Mauviel
A
A
Laboratoire de Biochimie du Tissu Conjonctif, C.H.U. Côte de Nacre, Caen, France.
Redini
F
F
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; D003094:Collagen / Q000096:biosynthesis*; D017308:Etodolac; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007210:Indoleacetic Acids / 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; D007210:Indoleacetic Acids; D007375:Interleukin-1; D017308:Etodolac; D003094:Collagen