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J Exp Med. 2010 Nov 22;207(12):2595-607. doi: 10.1084/jem.20100786. Epub 2010 Oct 25.

Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation.

Author information

1
Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA.

Abstract

Nogo-B is a member of the reticulon family of proteins (RTN-4B) that is highly expressed in lung tissue; however, its function remains unknown. We show that mice with Th2-driven lung inflammation results in a loss of Nogo expression in airway epithelium and smooth muscle compared with nonallergic mice, a finding which is replicated in severe human asthma. Mice lacking Nogo-A/B (Nogo-KO) display an exaggerated asthma-like phenotype, and epithelial reconstitution of Nogo-B in transgenic mice blunts Th2-mediated lung inflammation. Microarray analysis of lungs from Nogo-KO mice reveals a marked reduction in palate lung and nasal clone (PLUNC) gene expression, and the levels of PLUNC are enhanced in epithelial Nogo-B transgenic mice. Finally, transgenic expression of PLUNC into Nogo-KO mice rescues the enhanced asthmatic-like responsiveness in these KO mice. These data identify Nogo-B as a novel protective gene expressed in lung epithelia, and its expression regulates the levels of the antibacterial antiinflammatory protein PLUNC.

PMID:
20975041
PMCID:
PMC2989775
DOI:
10.1084/jem.20100786
[Indexed for MEDLINE]
Free PMC Article

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