Effect of benzylidene derivative (novel antirheumatic agent) on chondrocyte metabolism.
The effects of protocatechualdehyde (PAL), one of the metabolites of 3,4-diacetoxy benzylidene diacetate (ACP), on proteoglycan metabolism and secretion of interleukin 1 (IL-1) like activity (lymphocyte activating factor; LAF activity) were studied using rabbit articular chondrocytes culture under phorbol myristate acetate (PMA) and Ca2+ ionophore A23187 (A23187) or IL-1 alpha stimulation. In IL-1 alpha (20 u/ml) or PMA (0.1 micrograms/ml) and A23187 (0.2 micrograms/ml) treated culture of rabbit articular chondrocytes, PAL significantly reduced the degradation of 35S-proteoglycan (35S-PG) from the cells and matrix layers into the culture media in a dose dependent fashion without affecting proteoglycan synthesis. Similarly, the secretion or production of matrix metalloproteinases which degrade proteoglycans was also inhibited to the same extent under IL-1 alpha stimulated condition. However, PAL caused no effect on the secretion of IL-1 like activity by chondrocytes. These results suggest that an attractive candidate for an anti-inflammatory drug, ACP, which is a prodrug of PAL, has also a favorable action on chondrocyte metabolism in terms of proteoglycan degradation via inhibition of matrix metalloproteinases secretion or production.
Watanabe
K
K
Kureha Biomedical Research Laboratories, Tokyo, Japan.
Kimura
F
F
Shinmei
M
M
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology*; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D013462:Sulfur Radioisotopes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001547:Benzaldehydes; D002396:Catechols; D007375:Interleukin-1; D011509:Proteoglycans; D013462:Sulfur Radioisotopes; D000001:Calcimycin; C005581:protocatechualdehyde; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate