Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA.
J Exp Med. 2010 Nov 22;207(12):2595-607. doi: 10.1084/jem.20100786. Epub 2010 Oct 25.
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.
Nogo-B 是网抑素家族蛋白（RTN-4B）的成员，在肺组织中高度表达；但其功能尚不清楚。我们发现，与非过敏性小鼠相比，Th2 驱动的肺部炎症会导致气道上皮和平滑肌中 Nogo 表达的丧失，这一发现在严重的人类哮喘中得到了复制。缺乏 Nogo-A/B（Nogo-KO）的小鼠表现出哮喘样表型的过度表达，并且在转基因小鼠中上皮细胞中 Nogo-B 的重建会减弱 Th2 介导的肺部炎症。Nogo-KO 小鼠肺的基因芯片分析显示，腭肺和鼻克隆（PLUNC）基因的表达明显减少，而上皮细胞 Nogo-B 转基因小鼠中的 PLUNC 水平增强。最后，将 PLUNC 转染到 Nogo-KO 小鼠中可挽救这些 KO 小鼠中增强的哮喘样反应性。这些数据表明 Nogo-B 是一种在肺上皮细胞中表达的新型保护性基因，其表达调节抗菌抗炎蛋白 PLUNC 的水平。
