NLRP3 inflammasome triggers interleukin-37 release from human monocytes.
NLRP3 inflammasome triggers interleukin-37 release from human monocytes.
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NLRP3炎症体触发人单核细胞释放白介素37。
DOI：
10.1002/eji.202149724
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发表时间：
2022-07
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
IL - 37是IL - 1家族的抗炎成员，可抑制与许多非传染性疾病相关的炎症。然而，IL - 37的调控机制仍未得到充分研究。我们的目的是研究IL - 37的酶裂解，增强细胞外信号传导，以及IL - 37的分泌途径。在人类单核细胞中，成熟IL - 37 （mIL - 37）在NLRP3炎性体激活后释放。IL - 37的释放可通过抑制质膜通透性和气真皮蛋白- D -缺乏的THP - 1细胞来阻断。虽然发现IL - 37的分裂是组成性的，但在NLRP3缺失的THP - 1细胞中，以及在THP - 1和原代人单核细胞中，NLRP3抑制剂MCC950阻断了mIL - 37的释放。暴露于LPS 18小时后，IL - 37的分泌也发生了，与NLRP3炎性体无关。这种依赖LPS的IL - 37分泌需要质膜通透性，而不需要常规的蛋白质分泌装置。建议的caspase‐1切割位点（D20）或建议的替代切割位点（V46）的突变不能完全阻断IL‐37的加工。因此，我们提出了一种新的途径，在这种途径中，IL - 37被caspase - 1独立的机制切割，并通过不同的途径释放出典型的和替代的NLRP3炎症小体。答：在人单核细胞中，IL - 37分裂是组成性的，而不是在D20或V46位点。B.长期LPS刺激诱导成熟的IL - 37释放独立于替代NLRP3炎性体，但依赖于膜通透性。成熟的IL - 37释放是由典型NLRP3炎性体激活、气真皮蛋白D和膜通透性介导的。
IL‐37 is an anti‐inflammatory member of the IL‐1 family that dampens inflammation associated with many noncommunicable diseases. However, mechanisms of IL‐37 regulation remain understudied. We aimed to investigate the enzymatic cleavage of IL‐37 that potentiates extracellular signalling, as well as pathways of IL‐37 secretion. In human monocytes, mature IL‐37 (mIL‐37) was released following canonical NLRP3 inflammasome activation. The release of IL‐37 was blocked by inhibiting plasma membrane permeability and in gasdermin‐D‐deficient THP‐1 cells. While the cleavage of IL‐37 was found to be constitutive, the release of mIL‐37 was blocked in NLRP3‐deficient THP‐1 cells and by NLRP3 inhibitor MCC950 in THP‐1s and primary human monocytes. IL‐37 secretion also occurred after 18‐h exposure to LPS, independently of the alternative NLRP3 inflammasome. This LPS‐dependent IL‐37 secretion required plasma membrane permeability, but not conventional protein secretion apparatus. Mutagenesis of the suggested caspase‐1 cleavage site (D20) or the proposed alternative cleavage site (V46) did not completely block IL‐37 processing. Therefore, we propose a novel pathway in which IL‐37 is cleaved by caspase‐1‐independent mechanisms and released following canonical and alternative NLRP3 inflammasome triggers by differential pathways. A. In human monocytes, IL‐37 cleavage occurs constitutively but not at positions D20 or V46. B. Long‐term LPS stimulation induces mature IL‐37 release independently of alternative NLRP3 inflammasome but dependent on membrane permeability. C. Mature IL‐37 release is mediated by canonical NLRP3 inflammasome activation, gasdermin‐D, and membrane permeability.
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影响因子：
3.8
作者：
Kumar, S;Hanning, CR;Lotze, MT
通讯作者：
Lotze, MT
影响因子：
5.5
作者：
Rudloff, Ina;Cho, Steven X.;Nold, Marcel F.
通讯作者：
Nold, Marcel F.
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
7.3
作者：
Gritsenko A;Yu S;Martin-Sanchez F;Diaz-Del-Olmo I;Nichols EM;Davis DM;Brough D;Lopez-Castejon G
通讯作者：
Lopez-Castejon G
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影响因子：
4.6
作者：
Ji Q;Zeng Q;Huang Y;Shi Y;Lin Y;Lu Z;Meng K;Wu B;Yu K;Chai M;Liu Y;Zhou Y
通讯作者：
Zhou Y