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Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils

Programa de Pós-Graduação em Biologia Estrutural e Funcional, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil
Instituto de Química, Universidade Estadual de Campinas, Campinas 13083-862, São Paulo, Brazil
Laboratório de Pesquisa Multidisciplinar, Universidade São Francisco, Bragança Paulista 12916-900, São Paulo, Brazil
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
Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular, Universidade Federal de São Paulo, São Paulo 04044-010, Brazil
Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo 04044-020, Brazil
Author to whom correspondence should be addressed.
Cells 2021, 10(1), 121;
Received: 24 December 2020 / Revised: 5 January 2021 / Accepted: 6 January 2021 / Published: 11 January 2021
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-1β production by WT neutrophils after nigericin and ATP stimulation. However, IL-1β release was impaired in AnxA1-/- neutrophils stimulated by both agonists, and there was no further impairment in IL-1β 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-1β production by neutrophils, while endogenous AnxA1 is required for the activation of the NLRP3 machinery. View Full-Text
Keywords: Ac2-26; ATP; inflammation; mass spectrometry; nigericin; lipidomics Ac2-26; ATP; inflammation; mass spectrometry; nigericin; lipidomics
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MDPI and ACS Style

Sanches, J.M.; Correia-Silva, R.D.; Duarte, G.H.B.; Fernandes, A.M.A.P.; Sánchez-Vinces, S.; Carvalho, P.O.; Oliani, S.M.; Bortoluci, K.R.; Moreira, V.; Gil, C.D. Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils. Cells 2021, 10, 121.

AMA Style

Sanches JM, Correia-Silva RD, Duarte GHB, Fernandes AMAP, Sánchez-Vinces S, Carvalho PO, Oliani SM, Bortoluci KR, Moreira V, Gil CD. Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils. Cells. 2021; 10(1):121.

Chicago/Turabian Style

Sanches, José M., Rebeca D. Correia-Silva, Gustavo H.B. Duarte, Anna M.A.P. Fernandes, Salvador Sánchez-Vinces, Patrícia O. Carvalho, Sonia M. Oliani, Karina R. Bortoluci, Vanessa Moreira, and Cristiane D. Gil. 2021. "Role of Annexin A1 in NLRP3 Inflammasome Activation in Murine Neutrophils" Cells 10, no. 1: 121.

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