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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 10
[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
Total Affiliations: 7
Document type: Journal article
Source: CELLS; v. 11, n. 2 JAN 2022.
Web of Science Citations: 0

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 Conceição
Support type: 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 type: 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 type: Regular Research Grants