Antiinflammatory action of thielocin A1?, a group II phospholipase A2 specific inhibitor, in rat carrageenan-induced pleurisy

Abstract

Extracellular phospholipase A₂ (PLA₂) activity was detected in exudate from rat carrageenan-induced pleurisy using [³H]oleic acid-labeledEscherichia 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 Alβ, a novel type of PLA₂ inhibitor from fungi, inhibited this PLA₂-II activity in a dose-dependent manner (IC₅₀=0.32μM). Thielocin A1β 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 A1β had no effect on the PGE₂ content in the exudate. These results suggest that thielocin A1β shows antiinflammatory activity due to inhibition of PLA₂-II and offer evidence for the significance of PLA₂1I in the propagation of inflammatory processes.