Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation

Hai B. Tran, Martin D. Lewis, Lor Wai Tan, Susan E. Lester, Leonie M. Baker, Jia Ng, Monica A. Hamilton-Bruce, Catherine L. Hill, Simon A. Koblar, Maureen Rischmueller, Richard E. Ruffin, Peter J. Wormald, Peter D. Zalewski, Carol J. Lang

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1 β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1 β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1 β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1 β and TNF α . In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis.

Original languageEnglish
Title of host publicationJournal of Allergy
Pages1-13
Number of pages13
DOIs
Publication statusPublished or Issued - 18 Mar 2012

Publication series

NameJournal of Allergy
Volume2012

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