{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:35:04Z","timestamp":1789763704434,"version":"4.0.1"},"reference-count":81,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2020\/03565-2"],"award-info":[{"award-number":["2020\/03565-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Formyl 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-1\u03b2. 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.<\/jats:p>","DOI":"10.3390\/cells11020228","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models"],"prefix":"10.3390","volume":"11","author":[{"given":"Izabella","family":"Lice","sequence":"first","affiliation":[{"name":"Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo-UNIFESP, Sao Paulo 04023-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Marcos","family":"Sanches","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center, Department of Ophthalmology, Dallas, TX 75390-9057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca D.","family":"Correia-Silva","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo-UNIFESP, Sao Paulo 04023-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-6295","authenticated-orcid":false,"given":"Mab P.","family":"Corr\u00eaa","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Humanities and Exact Sciences, Universidade Estadual Paulista-UNESP, Sao Jose do Rio Preto 15054-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Y.","family":"Icimoto","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Universidade Federal de S\u00e3o Paulo-UNIFESP, Sao Paulo 04039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6400-5201","authenticated-orcid":false,"given":"Alex A. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, Sao Francisco University, Braganc\u0327a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-6544","authenticated-orcid":false,"given":"Salvador","family":"S\u00e1nchez-Vinces","sequence":"additional","affiliation":[{"name":"MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, Sao Francisco University, Braganc\u0327a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-8594","authenticated-orcid":false,"given":"Andreia M.","family":"Porcari","sequence":"additional","affiliation":[{"name":"MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, Sao Francisco University, Braganc\u0327a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-1967","authenticated-orcid":false,"given":"Vanessa","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo-UNIFESP, Sao Paulo 04044-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-4126","authenticated-orcid":false,"given":"Cristiane D.","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo-UNIFESP, Sao Paulo 04023-900, SP, Brazil"},{"name":"Institute of Biosciences, Humanities and Exact Sciences, Universidade Estadual Paulista-UNESP, Sao Jose do Rio Preto 15054-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.pharmthera.2010.04.010","article-title":"Therapeutic anti-inflammatory potential of formyl-peptide receptor agonists","volume":"127","author":"Dufton","year":"2010","journal-title":"Pharmacol. 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