Antiinflammatory action of thielocin A1 beta, a group II phospholipase A2 specific inhibitor, in rat carrageenan-induced pleurisy.
Extracellular phospholipase A2 (PLA2) activity was detected in exudate from rat carrageenan-induced pleurisy using [3H]oleic acid-labeled Escherichia coli as substrate. Both exudate volume and PLA2 activity increased up to 24 h after carrageenin injection. Specific absorption of this activity by anti-group II PLA2 (PLA2-II) antibody indicated that the PLA2 activity in the pleural exudate was PLA2-II. Thielocin A1 beta, a novel type of PLA2 inhibitor from fungi, inhibited this PLA2-II activity in a dose-dependent manner (IC50 = 0.32 microM). Thielocin A1 beta correspondingly reduced both exudate volume and PLA2-II activity in the exudate in a dose-dependent manner when coinjected with carrageenan. The exudate volume was also significantly decreased when indomethacin, a cyclooxygenase inhibitor, or dexamethasone, a steroidal antiinflammatory drug, was coinjected with carrageenan. However, neither indomethacin nor dexamethasone could significantly attenuate the PLA2-II activity in exudate. In addition, indomethacin and dexamethasone significantly reduced the levels of PGE2 in the exudate. However, thielocin A1 beta had no effect on the PGE2 content in the exudate. These results suggest that thielocin A1 beta shows antiinflammatory activity due to inhibition of PLA2-II and offer evidence for the significance of PLA2-II in the propagation of inflammatory processes.
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
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Tanaka
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Kato
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Matsumoto
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Yoshida
D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D010996:Pleural Effusion / Q000201:enzymology / Q000473:pathology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014966:Xanthenes / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014966:Xanthenes; C072738:thielocin A1beta; D002351:Carrageenan; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone