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

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

Author information

1
Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA.

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.

PMID:
23937860
PMCID:
PMC3751315
DOI:
10.1186/1743-8977-10-39
[Indexed for MEDLINE]
Free PMC Article

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