| Autor: |
Nanda, Sambit K, Prescott, Alan R, Figueras‐Vadillo, Clara, Cohen, Philip |
| Zdroj: |
EMBO Reports; 10/5/2021, Vol. 22 Issue 10, p1-14, 14p |
| Abstrakt: |
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. Synopsis: Formation of the NLRP3 inflammasome requires LPS to activate IKKβ and nigericin to disperse the trans‐Golgi network (TGN). IKKβ functions to recruit NLRP3 to the dispersed TGN promoting inflammasome formation and activation. The rapid formation of the NLRP3 inflammasome requires co‐stimulation with LPS and nigericin.LPS activates the protein kinase IKKβ, while nigericin triggers dispersion of the trans‐Golgi network independent of IKKβ.IKKβ activity is needed to recruit NLRP3 to the dispersed TGN.TGN recruitment is followed by inflammasome formation, caspase 1 and gasdermin D activation and IL‐1/‐18 secretion. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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