NLRP3/caspase-1-independent IL-1beta production mediates diesel exhaust particle-induced pulmonary inflammation.

  • Provoost S
  • Maes T
  • Pauwels N
 et al. 
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Abstract

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. IL-1beta/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-1beta into mature IL-1beta. In this study, we hypothesized that the NLRP3/caspase-1/IL-1beta 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-1beta neutralization impaired the DEP-induced lung inflammatory response. Upon DEP exposure, NLRP3 and caspase-1 knockout mice, however, showed similar IL-1beta 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-1beta/IL-1RI axis. In addition, DEP initiates inflammation independent of the classical NLRP3/caspase-1 pathway, suggesting that other proteases might be involved.

Author-supplied keywords

  • Animals
  • Carrier Proteins
  • Caspase 1
  • Cell Separation
  • Female
  • Flow Cytometry
  • Interleukin-1beta
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Pneumonia
  • Receptors, Interleukin-1 Type I
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Vehicle Emissions
  • biosynthesis
  • etiology
  • immunology
  • metabolism
  • toxicity

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Authors

  • Sharen Provoost

  • Tania Maes

  • Nele S Pauwels

  • Tom Vanden Berghe

  • Peter Vandenabeele

  • Bart N Lambrecht

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