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

被引：88

作者：

Hillegass, Jedd M. ^{[1
]}

Miller, Jill M. ^{[1
]}

MacPherson, Maximilian B. ^{[1
]}

Westbom, Catherine M. ^{[1
]}

Sayan, Mutlay ^{[1
]}

Thompson, Joyce K. ^{[1
]}

Macura, Sherrill L. ^{[1
]}

Perkins, Timothy N. ^{[1
]}

Beuschel, Stacie L. ^{[1
]}

Alexeeva, Vlada ^{[1
]}

Pass, Harvey I. ^{[2
]}

Steele, Chad ^{[3
]}

Mossman, Brooke T. ^{[1
]}

Shukla, Arti ^{[1
]}

机构：

[1] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA

[2] NYU, Sch Med, Langone Med Ctr, New York, NY USA

[3] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA

来源：

PARTICLE AND FIBRE TOXICOLOGY | 2013年 / 10卷

基金：

美国国家卫生研究院;

关键词：

Asbestos; Mesothelioma; Mesothelium; Inflammasomes; NLRP3; DNA-BINDING ACTIVITY; MALIGNANT MESOTHELIOMAS; MINERAL PATHOGENICITY; GENE-EXPRESSION; RAT LUNG; EXPOSURE; NECROSIS; PROTEIN; IL-1-BETA; GROWTH;

D O I：

10.1186/1743-8977-10-39

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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.

引用

页码：1 / 14

页数：14

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