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

Sanches, José Marcos LU ; Branco, Laura Migliari ; Duarte, Gustavo Henrique Bueno ; Oliani, Sonia Maria ; Bortoluci, Karina Ramalho ; Moreira, Vanessa and Gil, Cristiane Damas (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
; ; ; ; ; and
publishing date
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
2024-06-15 09:04:56
@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}},
}