Effects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models

dc.contributor.authorLice, Izabella
dc.contributor.authorSanches, José Marcos
dc.contributor.authorCorreia-Silva, Rebeca D.
dc.contributor.authorCorrêa, Mab P. [UNESP]
dc.contributor.authorIcimoto, Marcelo Y.
dc.contributor.authorSilva, Alex A. R.
dc.contributor.authorSánchez-Vinces, Salvador
dc.contributor.authorPorcari, Andreia M.
dc.contributor.authorMoreira, Vanessa
dc.contributor.authorGil, Cristiane D. [UNESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUT Southwestern Medical Center
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionSao Francisco University
dc.description.abstractFormyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1β. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation.en
dc.description.affiliationDepartment of Morphology and Genetics Universidade Federal de São Paulo-UNIFESP, SP
dc.description.affiliationUT Southwestern Medical Center Department of Ophthalmology
dc.description.affiliationInstitute of Biosciences Humanities and Exact Sciences Universidade Estadual Paulista-UNESP, SP
dc.description.affiliationDepartment of Biophysics Universidade Federal de São Paulo-UNIFESP, SP
dc.description.affiliationMS4Life Laboratory of Mass Spectrometry Health Sciences Postgraduate Program Sao Francisco University, SP
dc.description.affiliationDepartment of Pharmacology Universidade Federal de São Paulo-UNIFESP, SP
dc.description.affiliationUnespInstitute of Biosciences Humanities and Exact Sciences Universidade Estadual Paulista-UNESP, SP
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2019/04314-6
dc.description.sponsorshipIdFAPESP: 2019/15017-2
dc.description.sponsorshipIdFAPESP: 2020/03565-2
dc.identifier.citationCells, v. 11, n. 2, 2022.
dc.subjectAnnexin A1-derived peptides
dc.subjectSynthetic peptides
dc.titleEffects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Modelsen