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

Izabela GalvãoRenan Villanova Homem de CarvalhoJuliana P VagoAlexandre L N SilvaToniana G CarvalhoMaísa Mota AntunesFabiola M RibeiroGustavo Batista MenezesDario S ZamboniLirlândia P SousaMauro M Teixeira
Published in: Immunology (2020)
Annexins are well-known Ca2+ 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)-1β 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-1β release in vivo and in vitro. These effects were due to reduction of transcriptional levels of IL-1β, 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.
Keyphrases
  • nlrp inflammasome
  • anti inflammatory
  • immune response
  • cell death
  • gene expression
  • fatty acid
  • transcription factor
  • endoplasmic reticulum stress
  • heat shock protein
  • dna binding