| First Author | Hirota JA | Year | 2012 |
| Journal | J Allergy Clin Immunol | Volume | 129 |
| Issue | 4 | Pages | 1116-25.e6 |
| PubMed ID | 22227418 | Mgi Jnum | J:332271 |
| Mgi Id | MGI:6840172 | Doi | 10.1016/j.jaci.2011.11.033 |
| Citation | Hirota JA, et al. (2012) The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter. J Allergy Clin Immunol 129(4):1116-25.e6 |
| abstractText | 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-1beta 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-1beta. Exposure of Nlrp3(-/-) and wild-type mice to PM in vivo demonstrates NLRP3-dependent production of IL-1beta 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. |
