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REDUCTION OF HUMAN RECOMBINANT TYPE II PHOSPHOLIPASE A 2 AND PROSTAGLANDIN F 2α RELEASE BY MICROTUBULE DEPOLYMERIZING AGENTS
Author(s) -
Munns Mj,
King Rg,
Rice Ge
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03020.x
Subject(s) - colchicine , endocrinology , medicine , chinese hamster ovary cell , prostaglandin , arachidonic acid , prostaglandin e , chemistry , biology , biochemistry , receptor , enzyme
1. The present study examines the effects of the microtubule depolarizing agent colchicine on secretory type II phospholipase A 2 (PLA 2 ) function in Chinese hamster ovary (CHO) cells that specifically overexpress human type II PLA 2 and the effect of both colchicine and tubulazole on the release of type II PLA 2 and prostaglandin (PG) F 2α from human placental explants. 2. Significant suppression by colchicine (0.01–10 μmol/L) of PLA 2 activity ( P < 0.00001), immunoreactive type II PLA 2 (irPLA 2 ; P < 0.00001) and PGF 2α release ( P < 0.01) was observed in medium from overexpressing CHO cells. These effects were significantly reduced ( P < 0.0001) in the presence of 10 μmol/L taxol, an agent that prevents depolymerization of microtubules. The addition of 30 μmol/L arachidonic acid significantly reduced ( P < 0.0001) the inhibition of PGF 2α production in CHO cell lines. 3. The addition of 1 μmol/L colchicine to human placental explants for 24 h significantly reduced irPLA 2 ( P < 0.00001) and PGF 2α production ( P < 0.00001). Similarly, 1 μmol/L tubulazole significantly blocked irPLA 2 ( P < 0.001) and PGF 2α ( P < 0.0001). 4. At 10 μmol/L, taxol significantly reduced irPLA 2 inhibition by colchicine ( n = 8; P < 0.05) and tubulazole ( n = 8; P < 0.05). Similarly, taxol significantly reduced the reduction in PGF 2α production caused by colchicine ( P < 0.001) and by tubulazole ( P < 0.001). 5. These results suggest that integrity of the microtubule system is required for PLA 2 function and the subsequent production of pro‐inflammatory mediators.