Silica induces NLRP3 inflammasome activation in human lung epithelial cells

P.M. Peeters, T.N. Perkins, E.F.M. Wouters, B.T. Mossman, N.L. Reynaert*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


ABSTRACT: BACKGROUND: In myeloid cells the inflammasome plays a crucial innate immune defenses against pathogen- and danger-associated patterns crystalline silica. Respirable mineral particles impinge upon the lung causing irreversible damage, sustained inflammation and silicosis. In we investigated lung epithelial cells as a target for silica-induced activation. METHODS: A human bronchial epithelial cell line (BEAS-2B) normal human bronchial epithelial cells (NHBE) were exposed to toxic but nonlethal doses of crystalline silica over time to perform functional characterization of NLRP3, caspase-1, IL-1beta, bFGF and HMGB1. RT-PCR, caspase-1 enzyme activity assay, Western blot techniques, cytokine-specific ELISA and fibroblast (MRC-5 cells) proliferation performed. RESULTS: We were able to show transcriptional and upregulation of the components of the NLRP3 intracellular platform, as activation of caspase-1. NLRP3 activation led to maturation of pro-IL- secreted IL-1beta, and a significant increase in the unconventional the alarmins bFGF and HMGB1. Moreover, release of bFGF and HMGB1 was dependent on particle uptake. Small interfering RNA experiments using revealed the pivotal role of the inflammasome in diminished release of pro-inflammatory cytokines, danger molecules and growth factors, and proliferation. CONCLUSION: Our novel data indicate the presence and activation of the NLRP3 inflammasome by crystalline silica in human lung epithelial cells, which prolongs an inflammatory signal and affects proliferation, mediating a cadre of lung diseases.
Original languageEnglish
Article number3
JournalParticle and Fibre Toxicology
Issue number1
Publication statusPublished - 1 Jan 2013

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