IKKβ 对于 NLRP3 炎性小体的形成是必需的。
IKKβ is required for the formation of the NLRP3 inflammasome.
机构信息
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
Dundee Imaging Facility and Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
出版信息
EMBO Rep. 2021 Oct 5;22(10):e50743. doi: 10.15252/embr.202050743. Epub 2021 Aug 17.
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.
NLRP3 炎性小体的快速形成和激活是由 LPS 和 Nigericin 的共同刺激诱导的。它需要 LPS 刺激的 IKKβ 的激活，而 IKKβ 的激活不依赖于新基因转录、蛋白质翻译和 IKKβ 激活的其他蛋白激酶。IKKβ 不参与 Nigericin 诱导的转高尔基网络 (TGN) 的分散，但将 NLRP3 与 TGN38 接近。LPS 共同刺激增强了 Nigericin 诱导的高尔基体分散，这种增强依赖于 IKKβ。用 LPS 进行长时间刺激以增加 NLRP3 的表达，然后用 Nigericin 刺激，产生更大的 TGN38 阳性斑点，随后用 Nigericin 刺激前加入 IKKβ 抑制剂抑制了 NLRP3 炎性小体的激活。因此，IKKβ 在将 NLRP3 募集到分散的 TGN 中起着关键作用，导致 NLRP3 炎性小体的形成和激活。
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