NDLI: Airway Epithelium Controls Lung Inflammation and Injury through the NF-κB Pathway

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Airway Epithelium Controls Lung Inflammation and Injury through the NF-κB Pathway

Content Provider	Scilit
Author	Cheng, Dong-Sheng Han, Wei Chen, Sabrina M. Sherrill, Taylor P. Chont, Melissa Park, Gye-Young Sheller, James R. Polosukhin, Vasiliy V. Christman, John W. Yull, Fiona E. Blackwell, Timothy S.
Copyright Year	2007
Description	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-κB pathway signaling in airway epithelium could decisively impact inflammatory phenotypes in the lungs by using a tetracycline-inducible system to achieve selective NF-κB activation or inhibition in vivo. In transgenic mice that express a constitutively active form of IκB kinase 2 under control of the epithelial-specific CC10 promoter, treatment with doxycycline induced NF-κB 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-κB in airway epithelium prevented lung inflammation and injury resulting from expression of constitutively active form of IκB 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-κB 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.
Ending Page	6513
Page Count	10
Starting Page	6504
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.178.10.6504
Journal	The Journal of Immunology
Issue Number	10
Volume Number	178
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2007-05-15
Access Restriction	Open
Subject Keyword	Lung Inflammation Nf Κb Airway Epithelial Cells Iκb Kinase
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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