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Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils.
Sanches, José Marcos; Correia-Silva, Rebeca D; Duarte, Gustavo H B; Fernandes, Anna Maria A P; Sánchez-Vinces, Salvador; Carvalho, Patrícia O; Oliani, Sonia M; Bortoluci, Karina R; Moreira, Vanessa; Gil, Cristiane D.
Afiliación
  • Sanches JM; Programa de Pós-Graduação em Biologia Estrutural e Funcional, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil.
  • Correia-Silva RD; Programa de Pós-Graduação em Biologia Estrutural e Funcional, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil.
  • Duarte GHB; Instituto de Química, Universidade Estadual de Campinas, Campinas 13083-862, São Paulo, Brazil.
  • Fernandes AMAP; Laboratório de Pesquisa Multidisciplinar, Universidade São Francisco, Bragança Paulista 12916-900, São Paulo, Brazil.
  • Sánchez-Vinces S; Laboratório de Pesquisa Multidisciplinar, Universidade São Francisco, Bragança Paulista 12916-900, São Paulo, Brazil.
  • Carvalho PO; Laboratório de Pesquisa Multidisciplinar, Universidade São Francisco, Bragança Paulista 12916-900, São Paulo, Brazil.
  • Oliani SM; Programa de Pós-Graduação em Biologia Estrutural e Funcional, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil.
  • Bortoluci KR; Programa de Pós-Graduação em Biociências, Universidade Estadual Paulista (UNESP), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Preto 15054-000, São Paulo, Brazil.
  • Moreira V; Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular, Universidade Federal de São Paulo, São Paulo 04044-010, Brazil.
  • Gil CD; Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo 04044-020, Brazil.
Cells ; 10(1)2021 01 11.
Article en En | MEDLINE | ID: mdl-33440601
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-1ß production by WT neutrophils after nigericin and ATP stimulation. However, IL-1ß release was impaired in AnxA1-/- neutrophils stimulated by both agonists, and there was no further impairment in IL-1ß 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-1ß production by neutrophils, while endogenous AnxA1 is required for the activation of the NLRP3 machinery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Neutrófilos Límite: Animals Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Neutrófilos Límite: Animals Idioma: En Revista: Cells Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza