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Publication : The role of annexin A1 in the modulation of the NLRP3 inflammasome.

First Author  Galvão I Year  2020
Journal  Immunology Volume  160
Issue  1 Pages  78-89
PubMed ID  32107769 Mgi Jnum  J:298117
Mgi Id  MGI:6471232 Doi  10.1111/imm.13184
Citation  Galvao I, et al. (2020) The role of annexin A1 in the modulation of the NLRP3 inflammasome. Immunology 160(1):78-89
abstractText  Annexins are well-known Ca(2+) phospholipid-binding proteins, which have a wide variety of cellular functions. The role of annexin A1 (AnxA1) in the innate immune system has focused mainly on the anti-inflammatory and proresolving properties through its binding to the formyl-peptide receptor 2 (FPR2)/ALX receptor. However, studies suggesting an intracellular role of AnxA1 are emerging. In this study, we aimed to understand the role of AnxA1 for interleukin (IL)-1beta release in response to activators of the nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3) inflammasome. Using AnxA1 knockout mice, we observed that AnxA1 is required for IL-1beta release in vivo and in vitro. These effects were due to reduction of transcriptional levels of IL-1beta, NLRP3 and caspase-1, a step called NLRP3 priming. Moreover, we demonstrate that AnxA1 co-localize and directly bind to NLRP3, suggesting the role of AnxA1 in inflammasome activation is independent of its anti-inflammatory role via FPR2. Therefore, AnxA1 regulates NLRP3 inflammasome priming and activation in a FPR2-independent manner.
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