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.
Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA.
Paulette L
PL
Wright
Jun
J
Yu
Y P Peter
YP
Di
Robert J
RJ
Homer
Geoffrey
G
Chupp
Jack A
JA
Elias
Lauren
L
Cohn
William C
WC
Sessa
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