References
Query Results -- Details
MGI Accession ID: MGI:3836698
J Number: J:146109
Other Accession IDs:
Title: Airway epithelium controls lung inflammation and injury through the NF-kappa B pathway.
Authors: Cheng DS; Han W; Chen SM; Sherrill TP; Chont M; Park GY; Sheller JR; Polosukhin VV; Christman JW; Yull FE; Blackwell TS
Journal: J Immunol
Volume: 178
Issue: 10
Date: 2007 May 15
Year: 2007
Pages: 6504-13
Review Status: Peer Reviewed
Abstract:
Although airway epithelial cells provide important barrier and host defense functions, a crucial role for these cells in development of acute lung inflammation and injury has not been elucidated. We investigated whether NF-kappaB pathway signaling in airway epithelium could decisively impact inflammatory phenotypes in the lungs by using a tetracycline-inducible system to achieve selective NF-kappaB activation or inhibition in vivo. In transgenic mice that express a constitutively active form of IkappaB kinase 2 under control of the epithelial-specific CC10 promoter, treatment with doxycycline induced NF-kappaB activation with consequent production of a variety of proinflammatory cytokines, high-protein pulmonary edema, and neutrophilic lung inflammation. Continued treatment with doxycycline caused progressive lung injury and hypoxemia with a high mortality rate. In contrast, inducible expression of a dominant inhibitor of NF-kappaB in airway epithelium prevented lung inflammation and injury resulting from expression of constitutively active form of IkappaB kinase 2 or Escherichia coli LPS delivered directly to the airways or systemically via an osmotic pump implanted in the peritoneal cavity. Our findings indicate that the NF-kappaB pathway in airway epithelial cells is critical for generation of lung inflammation and injury in response to local and systemic stimuli; therefore, targeting inflammatory pathways in airway epithelium could prove to be an effective therapeutic strategy for inflammatory lung diseases.
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