title: FPRL1-mediated induction of superoxide in LL-37-stimulated IMR90 human fibroblast.
abstract: Molecular mechanisms underlying the generation of reactive oxygen species in LL-37-stimulated cells are poorly understood. Previously, we demonstrated that in human fibroblasts the exposure to WKYMVm induced p47(phox) phosphorylation and translocation and, in turn, NADPH oxidase activation. These effects were mediated by the activation of the Formyl-peptide receptor-like 1 (FPRL1) and the downstream signaling involved ERKs phosphorylation and PKCalpha- and PKCdelta-activation. Since LL-37 uses FPRL1 as a receptor to mediate its action on several cell types, we investigated in LL-37-stimulated IMR90 cells molecular mechanisms involved in NADPH-dependent superoxide generation. The exposure to LL-37, which is expressed in fibroblasts, induced ERKs activation, p47(phox) phosphorylation and translocation as well as NADPH oxidase activation. These effects were prevented by pertussis toxin, PD098059 and WRWWWW, a FPRL1-selective antagonist. Furthermore, the stimulation with LL-37 of HEK293 cells, transfected to stably express FPRL1, induced a rapid activation of ERKs and p47(phox) phosphorylation.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Iaccio
authors.forename: Fabio
authors.initials: F
authors.lastname: Cattaneo
authors.forename: Martina
authors.initials: M
authors.lastname: Mauro
authors.forename: Rosario
authors.initials: R
authors.lastname: Ammendola
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D021381:Protein Transport; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C105101:FPR2 protein, human; D005419:Flavonoids; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C509690:tryptophyl-arginyl-tryptophyl-tryptophyl-tryptophyl-tryptophanamide; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D054804:Cathelicidins