FPRL1-mediated induction of superoxide in LL-37-stimulated IMR90 human fibroblast |
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Authors: | Iaccio Annalisa Cattaneo Fabio Mauro Martina Ammendola Rosario |
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Institution: | a Dipartimento S.T.A.T., Università del Molise, Contrada Fonte Lappone, 86090 Pesche (IS), Italy b Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy |
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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 p47phox 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 PKCα- and PKCδ-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, p47phox 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 p47phox phosphorylation. |
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Keywords: | Reactive oxygen species Human fibroblasts NADPH oxidase FPRL1 LL-37 ERKs p47phox |
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