Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages

Author(s)

Sanches, Jose Marcos ^{[1, 2]} ; Branco, Laura Migliari ^{[3, 4]} ; Bueno Duarte, Gustavo Henrique ^[5] ; Oliani, Sonia Maria ^[6] ; Bortoluci, Karina Ramalho ^{[3, 4]} ; Moreira, Vanessa ^[7] ; Gil, Cristiane Damas ^{[1, 6]}

Affiliation

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

^[2] Univ Oeste Paulista, Fac Med, BR-11410980 Guaruja, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Ciencias Biol, BR-04044010 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol, BR-04044010 Sao Paulo - Brazil

^[5] Univ Estadual Campinas, Inst Quim, BR-13083862 Campinas, SP - Brazil

^[6] Univ Estadual Paulista, Programa Posgrad Biociencias, Inst Biociencias Letras & Ciencias Exatas IBILCE, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

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

• Document type: Journal article
• Source: CELLS; v. 9, n. 4 APR 2020.
• Web of Science Citations: 0

Abstract

Annexin A1 (AnxA1) is a potent anti-inflammatory protein that downregulates proinflammatory cytokine release. This study evaluated the role of AnxA1 in the regulation of NLRP3 inflammasome activation and lipid release by starch-elicited murine peritoneal macrophages. C57bl/6 wild-type (WT) and AnxA1-null (AnxA1(-/-)) mice received an intraperitoneal injection of 1.5% starch solution for macrophage recruitment. NLRP3 was activated by priming cells with lipopolysaccharide for 3 h, followed by nigericin (1 h) or ATP (30 min) incubation. As expected, nigericin and ATP administration decreased elicited peritoneal macrophage viability and induced IL-1 beta release, more pronounced in the AnxA1(-/-) cells than in the control peritoneal macrophages. In addition, nigericin-activated AnxA1(-/-) macrophages showed increased levels of NLRP3, while points of co-localization of the AnxA1 protein and NLRP3 inflammasome were detected in WT cells, as demonstrated by ultrastructural analysis. The lipidomic analysis showed a pronounced release of prostaglandins in nigericin-stimulated WT peritoneal macrophages, while ceramides were detected in AnxA1(-/-) cell supernatants. Different eicosanoid profiles were detected for both genotypes, and our results suggest that endogenous AnxA1 regulates the NLRP3-derived IL-1 beta and lipid mediator release in macrophages. (AU)

• FAPESP's process: 16/02012-4 - Evaluation of the immunomodulatory activity of annexin A1 protein in the regulation of inflammatory disorders of the gastrointestinal system: studies in vivo and in vitro experimental models
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/26872-5 - Study of anti-inflammatory and proinflammatory proteins as possible therapeutic targets in experimental models of neuroinflammation and cutaneous inflammation
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants