Inactivation of IκB-kinase-β dependent genes in airway epithelium reduces tobacco smoke induced acute airway inflammation

Sang Yeub Lee, Marina Miller, Jae Youn Cho, Dae Jin Song, Michael Karin, David H. Broide

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)

    Abstract

    We have examined the role of NF-κB regulated genes in airway epithelium in mediating tobacco smoke induced airway inflammation in studies of CC10-Cretg/IkkβΔ/Δ mice in which NF-κB signaling through IκB-kinase-β (IKK-β) is selectively ablated in epithelial cells in the airway. CC10-Cretg/IkkβΔ/Δ mice exposed to tobacco smoke for seven days had a significant decrease in the number of BAL cells (total cells, neutrophils, and macrophages) as well as significantly reduced numbers of peribronchial cells (F4/80+ and myeloperoxidase+) compared to tobacco exposed WT mice. In addition to the reduction in peribronchial cells, CC10-Cretg/IkkβΔ/Δ mice exposed to tobacco smoke had a significant decrease in the number of macrophages and neutrophils in the alveolar space suggesting that inactivation of NF-κB in the airway epithelium influenced the number of neutrophils and macrophages recruited to the alveolus. Levels of the NF-κB regulated chemokines KC and MCP-1 were significantly reduced in lungs of tobacco smoke exposed CC10-Cretg/IkkβΔ/Δ mice compared to tobacco exposed WT mice. In contrast, there was no significant difference in levels of NF-κB regulated MIP-1α between CC10-Cretg/IkkβΔ/Δ and WT mice. Lung sections of tobacco smoke exposed CC10-Cretg/IkkβΔ/Δ mice immunostained with KC or MCP-1 antibodies demonstrated reduced expression of these chemokines in the airway epithelium, but not in alveolar epithelium. Overall, these studies demonstrate an important role for NF-κB regulated genes in airway epithelium in contributing to acute tobacco smoke induced airway inflammation not only in the peribronchial space but also in the alveolar space.

    Original languageEnglish
    Pages (from-to)906-912
    Number of pages7
    JournalInternational Immunopharmacology
    Volume10
    Issue number8
    DOIs
    Publication statusPublished - 2010 Aug

    Keywords

    • Chemokines
    • Macrophage
    • Neutrophil

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Pharmacology

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