Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation.
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.
Wright
Paulette L
PL
Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA.
Yu
Jun
J
Di
Y P Peter
YP
Homer
Robert J
RJ
Chupp
Geoffrey
G
Elias
Jack A
JA
Cohn
Lauren
L
Sessa
William C
WC
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000032:analysis / Q000502:physiology*; D000070798:Nogo Proteins; D010750:Phosphoproteins / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*
C485599:BPIFA1 protein, human; D006023:Glycoproteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D010750:Phosphoproteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse