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Title
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NLRP3/Caspase-1-Independent IL-1β production mediates diesel exhaust particle-induced pulmonary inflammation
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Author
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Abstract
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| Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. IL-1 beta/IL-1RI signaling is crucial in several lung inflammatory responses. Typically, caspase-1 is activated within the NLRP3 inflammasome that recognizes several damage-associated molecular patterns, which results in cleavage of pro-IL-1 beta into mature IL-1 beta. In this study, we hypothesized that the NLRP3/caspase-1/IL-1 beta pathway is critical in DEP-induced lung inflammation. Upon DEP exposure, IL-1RI knockout mice had reduced pulmonary inflammation compared with wild-type mice. Similarly, treatment with rIL-1R antagonist (anakinra) and IL-1 beta neutralization impaired the DEP-induced lung inflammatory response. Upon DEP exposure, NLRP3 and caspase-1 knockout mice, however, showed similar IL-1 beta levels and comparable pulmonary inflammation compared with wild-type mice. In conclusion, these data show that the DEP-induced pulmonary inflammation acts through the IL-1 beta/IL-1RI axis. In addition, DEP initiates inflammation independent of the classical NLRP3/caspase-1 pathway, suggesting that other proteases might be involved. The Journal of Immunology, 2011, 187: 3331-3337. |
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Language
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English
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Source (journal)
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The journal of immunology. - Baltimore, Md
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Publication
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Baltimore, Md
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2011
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ISSN
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0022-1767
[Print]
1550-6606
[Online]
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DOI
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10.4049/JIMMUNOL.1004062
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Volume/pages
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187
:6
(2011)
, p. 3331-3337
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ISI
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000295034200052
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Full text (Publisher's DOI)
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