Sanches, Jose Marcos
Correia-Silva, Rebeca D.
Correa, Mab P.
Icimoto, Marcelo Y.
Silva, Alex A. R.
Porcari, Andreia M.
Gil, Cristiane D.
[1, 3, 7]
Total Authors: 10
 Univ Fed Sao Paulo UNIFESP, Dept Morphol & Genet, BR-04023900 Sao Paulo, SP - Brazil
 UT Southwestern Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 - USA
 Univ Estadual Paulista UNESP, Inst Biosci Humanities & Exact Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
 Univ Estadual Paulista UNESP, Dept Biophys, BR-04039032 Sao Paulo, SP - Brazil
 Sao Francisco Univ, Hlth Sci Postgrad Program, MS4Life Lab Mass Spectrometry, BR-12916900 Braganca Paulista, SP - Brazil
 Univ Fed Sao Paulo UNIFESP, Dept Pharmacol, BR-04044020 Sao Paulo, SP - Brazil
 Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Rua Botucatu 740, Ed Lemos Torres 3 Andar, BR-04023900 Sao Paulo, SP - Brazil
Total Affiliations: 7
Web of Science Citations:
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 beta. 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. (AU)