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

Abstract：

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.

journal_name

Part Fibre Toxicol

journal_title

Particle and fibre toxicology

authors

Hillegass JM,Miller JM,MacPherson MB,Westbom CM,Sayan M,Thompson JK,Macura SL,Perkins TN,Beuschel SL,Alexeeva V,Pass HI,Steele C,Mossman BT,Shukla A

doi

10.1186/1743-8977-10-39

subject

Has Abstract

pub_date

2013-08-13 00:00:00

pages

39

issn

1743-8977

pii

1743-8977-10-39

journal_volume

10

pub_type

杂志文章

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