Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils

Autor(es)

Sanches, Jose Marcos ^[1] ; Correia-Silva, Rebeca D. ^[1] ; Duarte, Gustavo H. B. ^[2] ; Fernandes, Anna Maria A. P. ^[3] ; Sanchez-Vinces, Salvador ^[3] ; Carvalho, Patricia O. ^[3] ; Oliani, Sonia M. ^{[1, 4]} ; Bortoluci, Karina R. ^{[5, 6]} ; Moreira, Vanessa ^[7] ; Gil, Cristiane D. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Programa Posgrad Biol Estrut & Func, BR-04023900 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Inst Quim, BR-13083862 Campinas, SP - Brazil

^[3] Univ Sao Francisco, Lab Pesquisa Multidisciplinar, BR-12916900 Braganca Paulista, SP - Brazil

^[4] Univ Estadual Paulista UNESP, Inst Biociencias Letras & Ciencias Exatas, Programa Posgrad Biociencias, BR-15054000 Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Dept Ciencias Biol, BR-04044010 Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol, BR-04044010 Sao Paulo - Brazil

^[7] Univ Fed Sao Paulo, Dept Farmacol, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 10, n. 1 JAN 2021.
• Citações Web of Science: 0

Resumo

This study evaluated the role of endogenous and exogenous annexin A1 (AnxA1) in the activation of the NLRP3 inflammasome in isolated peritoneal neutrophils. C57BL/6 wild-type (WT) and AnxA1 knockout mice (AnxA1(-/-)) received 0.3% carrageenan intraperitoneally and, after 3 h, the peritoneal exudate was collected. WT and AnxA1(-/-) neutrophils were then stimulated with lipopolysaccharide, followed by the NLRP3 agonists nigericin or ATP. To determine the exogenous effect of AnxA1, the neutrophils were pretreated with the AnxA1-derived peptide Ac2-26 followed by the NLRP3 agonists. Ac2-26 administration reduced NLRP3-derived IL-1 beta production by WT neutrophils after nigericin and ATP stimulation. However, IL-1 beta release was impaired in AnxA1(-/-) neutrophils stimulated by both agonists, and there was no further impairment in IL-1 beta release with Ac2-26 treatment before stimulation. Despite this, ATP- and nigericin-stimulated AnxA1(-/-) neutrophils had increased levels of cleaved caspase-1. The lipidomics of supernatants from nigericin-stimulated WT and AnxA1(-/-) neutrophils showed potential lipid biomarkers of cell stress and activation, including specific sphingolipids and glycerophospholipids. AnxA1 peptidomimetic treatment also increased the concentration of phosphatidylserines and oxidized phosphocholines, which are lipid biomarkers related to the inflammatory resolution pathway. Together, our results indicate that exogenous AnxA1 negatively regulates NLRP3-derived IL-1 beta production by neutrophils, while endogenous AnxA1 is required for the activation of the NLRP3 machinery. (AU)

• Processo FAPESP: 20/03565-2 - Efeito da anexina A1 e de seus peptídeos miméticos em modelos de resposta inflamatória in vitro (2D e 3D) e de toxicidade aguda in vivo
• Beneficiário: Cristiane Damas Gil
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/19949-7 - Avaliação da atividade imunomoduladora da proteína anexina A1 em lesões cutâneas e placentárias resultantes do Diabetes Mellitus
• Beneficiário: Sonia Maria Oliani
• Modalidade de apoio: Auxílio à Pesquisa - Regular