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

Author(s)

Lice, Izabella ^[1] ; Sanches, Jose Marcos ^[2] ; Correia-Silva, Rebeca D. ^[1] ; Correa, Mab P. ^[3] ; Icimoto, Marcelo Y. ^[4] ; Silva, Alex A. R. ^[5] ; Sanchez-Vinces, Salvador ^[5] ; Porcari, Andreia M. ^[5] ; Moreira, Vanessa ^[6] ; Gil, Cristiane D. ^{[1, 3, 7]}

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, Dept Morphol & Genet, BR-04023900 Sao Paulo, SP - Brazil

^[2] UT Southwestern Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 - USA

^[3] Univ Estadual Paulista UNESP, Inst Biosci Humanities & Exact Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Estadual Paulista UNESP, Dept Biophys, BR-04039032 Sao Paulo, SP - Brazil

^[5] Sao Francisco Univ, Hlth Sci Postgrad Program, MS4Life Lab Mass Spectrometry, BR-12916900 Braganca Paulista, SP - Brazil

^[6] Univ Fed Sao Paulo UNIFESP, Dept Pharmacol, BR-04044020 Sao Paulo, SP - Brazil

^[7] Univ Fed Sao Paulo UNIFESP, Dept Morfol & Genet, Rua Botucatu 740, Ed Lemos Torres 3 Andar, BR-04023900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 11, n. 2 JAN 2022.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 19/15017-2 - Biological effect of annexin A1-derived peptides in in vitro models of inflammation
• Grantee: Izabella Lice Moura
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/03565-2 - Effect of annexin A1 and its mimetic peptides in models of inflammatory response in vitro (2D and 3D) and acute toxicity in vivo
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/04314-6 - Imaging and mass spectrometry-based metabolomics applied to the study of drug resistance in neoadjuvant therapy for breast cancer: the search for a predictive test
• Grantee: Andréia de Melo Porcari
• Support Opportunities: Regular Research Grants