石棉和毛沸石首先激活 NLRP3 炎性小体，刺激人间皮细胞自分泌细胞因子释放。

Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells.

机构信息

Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA.

出版信息

Part Fibre Toxicol. 2013 Aug 13;10:39. doi: 10.1186/1743-8977-10-39.

BACKGROUND

Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear.

RESULTS

We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model.

CONCLUSIONS

These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.

背景

胸膜纤维化和恶性间皮瘤（MM）发生在接触致病性纤维后，但引发这些疾病的机制尚不清楚。

结果

我们记录了石棉和毛沸石对人胸膜间皮细胞中 NLRP3 炎性体的引发和激活，这与白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和血管内皮生长因子（VEGF）的释放有关。使用 Anakinra（一种白细胞介素-1 受体拮抗剂），可以在体外抑制这些蛋白的转录和释放，该拮抗剂在人腹膜 MM 小鼠异种移植模型中减少这些细胞因子的释放。