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

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 4; p. 926
• Main Authors: Sanches, José Marcos, Branco, Laura Migliari, Duarte, Gustavo Henrique Bueno, Oliani, Sonia Maria, Bortoluci, Karina Ramalho, Moreira, Vanessa, Gil, Cristiane Damas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 09.04.2020; MDPI AG
• Subjects: Animals; Annexin A1 - immunology; Annexin A1 - metabolism; Inflammasomes - immunology; Inflammasomes - metabolism; inflammation; Lipid Metabolism; lipidomics; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Male; mass spectrometry; Mice; Mice, Inbred C57BL; nigericin; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; pyroptosis; pyroptosis; mass spectrometry; inflammation; lipidomics; nigericin
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9040926

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-1β 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-1β and lipid mediator release in macrophages.