IKKβ is required for the formation of the NLRP3 inflammasome

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 IKK beta, which exerts its effects independently of de novo gene transcription, protein translation and other protein kinases activated by IKK beta. IKK beta 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 IKK beta-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 IKK beta inhibitors added prior to stimulation with nigericin. IKK beta therefore has a key role in recruiting NLRP3 to the dispersed TGN, leading to the formation and activation of the NLRP3 inflammasome.

Automated summary

The rapid formation and activation of the NLRP3 inflammasome is induced by co-stimulation with LPS and nigericin. IKK beta plays a crucial role in recruiting NLRP3 to the dispersed TGN, leading to the formation and activation of the NLRP3 inflammasome.