title: Suppression of inflammatory responses by surfactin, a selective inhibitor of platelet cytosolic phospholipase A2.
abstract: Surfactin inhibits platelet and spleen cytosolic 100 kDa phospholipase A2 (PLA2). In contrast, this same compound enhances rat platelet group II PLA2 activity by approximately 2-fold and slightly increases group I PLA2 activity from porcine pancreas and Naja naja venom in vitro. Surfactin does not affect a Ca2+ -independent PLA2 partially purified from bovine brain. Thus, this compound inhibits selectively the cytosolic form of PLA2. Based on in vitro studies utilizing preincubation of surfactin with the enzyme, dialysis, and increased concentrations of substrates, the inhibitory effect of surfactin appears to be due to a direct interaction with the enzyme. Linear regression analysis of the linear portion of a concentration-response curve reveals an IC50 of 8.5 microM. To further determine the inhibitory pattern, a Dixon plot was constructed to show that the inhibition by surfactin is competitive, but not uncompetitive, with an inhibition constant of Ki = 4.7 microM in 50 mM Tris-HCl buffer, pH 8.0, at 37 degrees. Surfactin blocked non-stimulated and calcium ionophore A23187-stimulated release of arachidonic acid from monkey kidney CV-1 cells, which contain a cytosolic 100 kDa PLA2 as the major activity, as shown in an anionic exchange DEAE-5PW high performance liquid chromatography profile and western blotting analysis. Surfactin ameliorated inflammation induced by several chemicals. That is, it exhibited in vivo anti-inflammatory activity in several tested inflammatory reactions including 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, carrageenan-induced rat paw edema, and acetic acid-induced mouse writhing. These results demonstrate that surfactin is a selective inhibitor for cytosolic PLA2 and a putative anti-inflammatory agent through the inhibitory effect produced by direct interaction with cytosolic PLA2, and that inhibition of cytosolic PLA2 activity may suppress inflammatory responses.
authors.affiliation: R & D Center, Cheil Jedang Corporation, Kyonggi-Do, South Korea.
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Jung
authors.forename: D K
authors.initials: DK
authors.lastname: Lee
authors.forename: J K
authors.initials: JK
authors.lastname: Jung
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
mesh_terms: D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000882:Haplorhini; D007249:Inflammation / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D055666:Lipopeptides; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010456:Peptides, Cyclic; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D055666:Lipopeptides; D010456:Peptides, Cyclic; C009365:surfactin peptide; D016718:Arachidonic Acid; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D019342:Acetic Acid