IKKβ is required for the formation of the NLRP3 inflammasome

Sambit Nanda (Lead / Corresponding author), Alan Prescott, Clara Figueras-Vadillo, Philip Cohen (Lead / Corresponding author)

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Abstract

The rapid formation and activation of the NLRP3 inflammasome is induced by co-stimulation with LPS and nigericin. It requires the LPS-stimulated activation of IKKβ, which exerts its effects independently of de novo gene transcription, protein translation and other protein kinases activated by IKKβ. IKKβ is not required for the nigericin-induced dispersion of the trans-Golgi network (TGN), but to bring NLRP3 in proximity with TGN38. The nigericin-induced dispersion of the Golgi is enhanced by co-stimulation with LPS, and this enhancement is IKKβ-dependent. Prolonged stimulation with LPS to increase the expression of NLRP3, followed by stimulation with nigericin, produced larger TGN38-positive puncta, and the ensuing activation of the NLRP3 inflammasome was also suppressed by IKKβ inhibitors added prior to stimulation with nigericin. IKKβ therefore has a key role in recruiting NLRP3 to the dispersed TGN, leading to the formation and activation of the NLRP3 inflammasome.
Original languageEnglish
Article numbere50743
Number of pages14
JournalEMBO Reports
Early online date17 Aug 2021
DOIs
Publication statusE-pub ahead of print - 17 Aug 2021

Keywords

  • inflammasome
  • innate immunity
  • kinases
  • toll-like receptors
  • trans-golgi network

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