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

• Autor(a) principal: Sanches, Jose Marcos
• Data de Publicação: 2020
• Outros Autores: Branco, Laura Migliari, Bueno Duarte, Gustavo Henrique, Oliani, Sonia Maria [UNESP], Bortoluci, Karina Ramalho, Moreira, Vanessa, Gil, Cristiane Damas [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.3390/cells9040926; http://hdl.handle.net/11449/197794
• topic: inflammation; nigericin; pyroptosis; mass spectrometry; lipidomics

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.