The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter

J Allergy Clin Immunol. 2012 Apr;129(4):1116-25.e6. doi: 10.1016/j.jaci.2011.11.033. Epub 2012 Jan 9.


Background: The airway epithelium is the first line of defense against inhaled insults and therefore must be capable of coordinating appropriate inflammatory and immune responses.

Objective: We sought to test the hypothesis that the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, an intracellular danger-sensing complex, plays a critical role in airway epithelium-mediated immune responses to urban particulate matter (PM) exposure.

Methods: In this study we (1) identified NLRP3 and caspase-1 expression in human airway epithelium bronchus and primary cells, (2) characterized NLRP3 inflammasome-mediated IL-1β production from human airway epithelium in response to PM, and (3) performed in vivo PM exposure experiments with wild-type and Nlrp3(-/-) mice.

Results: Our results demonstrate that human airway epithelium contains a functional NLRP3 inflammasome that responds to PM exposure with caspase-1 cleavage and production of IL-1β. Exposure of Nlrp3(-/-) and wild-type mice to PM in vivo demonstrates NLRP3-dependent production of IL-1β in the lung, airway neutrophilia, and increases in CD11c(+hi)/MHC class II(+hi) cell numbers in intrathoracic lymph nodes.

Conclusion: Our study is the first to characterize airway epithelial NLRP3 inflammasome-mediated immune responses to PM exposure, which might have implications in patients with asthma and other lung diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Humans
  • Immunophenotyping
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism
  • Leucine-Rich Repeat Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Particulate Matter / immunology*
  • Protein Transport
  • Proteins / genetics
  • Proteins / metabolism*
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism*


  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Leucine-Rich Repeat Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Particulate Matter
  • Proteins