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

Academic Article

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. © 2013 Hillegass et al.; licensee BioMed Central Ltd.
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    Digital Object Identifier (doi)

    Author List

  • Hillegass JM; Miller JM; MacPherson MB; Westbom CM; Sayan M; Thompson JK; Macura SL; Perkins TN; Beuschel SL; Alexeeva V
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  • 1
  • End Page

  • 14
  • Volume

  • 10
  • Issue

  • 1