Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages
(2020) In Cells 9(4).- 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-1β release, more pronounced in the AnxA1-/- cells than in the control peritoneal macrophages. In... (More)
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.
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- author
- Sanches, José Marcos LU ; Branco, Laura Migliari ; Duarte, Gustavo Henrique Bueno ; Oliani, Sonia Maria ; Bortoluci, Karina Ramalho ; Moreira, Vanessa and Gil, Cristiane Damas
- publishing date
- 2020-04-09
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Annexin A1/immunology, Inflammasomes/immunology, Lipid Metabolism, Macrophages, Peritoneal/immunology, Male, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- in
- Cells
- volume
- 9
- issue
- 4
- publisher
- MDPI AG
- external identifiers
-
- scopus:85083360665
- pmid:32283822
- ISSN
- 2073-4409
- DOI
- 10.3390/cells9040926
- language
- English
- LU publication?
- no
- id
- b574f018-f539-4ca1-9da0-cac04248cddc
- date added to LUP
- 2021-03-31 14:05:02
- date last changed
- 2024-09-07 17:08:56
@article{b574f018-f539-4ca1-9da0-cac04248cddc, abstract = {{<p>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.</p>}}, author = {{Sanches, José Marcos and Branco, Laura Migliari and Duarte, Gustavo Henrique Bueno and Oliani, Sonia Maria and Bortoluci, Karina Ramalho and Moreira, Vanessa and Gil, Cristiane Damas}}, issn = {{2073-4409}}, keywords = {{Animals; Annexin A1/immunology; Inflammasomes/immunology; Lipid Metabolism; Macrophages, Peritoneal/immunology; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism}}, language = {{eng}}, month = {{04}}, number = {{4}}, publisher = {{MDPI AG}}, series = {{Cells}}, title = {{Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages}}, url = {{http://dx.doi.org/10.3390/cells9040926}}, doi = {{10.3390/cells9040926}}, volume = {{9}}, year = {{2020}}, }