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Activation of the 7 nAChR Reduces Acid-Induced Acute Lung Injury in Mice and Rats

Cardiovascular Research Institute, University of California, San Francisco, California; and Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Correspondence and requests for reprints should be addressed to Xiao Su, M.D., Ph.D., Cardiovascular Research Institute, University of California San Francisco, HSW 825, 505 Parnassus Ave., San Francisco, CA 94143–0130. E-mail: xiao.su{at}ucsf.edu

New evidence indicates that neural mechanisms can down-regulate acute inflammation. In these studies, we tested the potential role of the 7 nicotinic acetylcholine receptor (7 nAChR) in a rodent model of acid-induced acute lung injury. We first determined that the 7 nAChR was expressed by alveolar macrophages and lung epithelial cells. Then, using an acid-induced acute lung injury mouse model, we found that nicotine, choline, and PNU-282987 (a specific 7 nAChR agonist) decreased excess lung water and lung vascular permeability, and reduced protein concentration in the bronchoalveolar lavage (BAL). Deficiency of 7 nAChR resulted in a 2-fold increase in excess lung water and lung vascular permeability. The reduction of proinflammatory cytokines (macrophage inflammatory protein-2 and TNF-) in the BAL with nicotine probably resulted from the suppression of NF-B activation in alveolar macrophages. The beneficial effect of nicotine was also tested in rat model of acid-induced acute lung injury in which BAL protein and receptor for advanced glycation end products (RAGE), a marker of type I cell injury, were reduced by nicotine treatment. These results indicate that activation of 7 nAChR may provide a new therapeutic pathway for the treatment of acute lung injury.

Key Words: 7 nicotinic acetylcholine receptor • acute lung injury • alveolar macrophage • nicotine • proinflammatory cytokines

CLINICAL RELEVANCE Activation of 7 nAChR down-regulates proinflammatory responses. Stimulation of pathway may provide a new therapeutic pathway for the treatment of acute lung injury.

 

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