期刊
PARTICLE AND FIBRE TOXICOLOGY
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1743-8977-10-39
关键词
Asbestos; Mesothelioma; Mesothelium; Inflammasomes; NLRP3
类别
资金
- National Institutes of Health [R01 ES021110, T32 ES007122]
- Lake Champlain Cancer Research Organization (LCCRO), Burlington, VT
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-1 beta, 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.
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