title: Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and rats.
abstract: New evidence indicates that neural mechanisms can down-regulate acute inflammation. In these studies, we tested the potential role of the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) in a rodent model of acid-induced acute lung injury. We first determined that the alpha7 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-282,987 (a specific alpha7 nAChR agonist) decreased excess lung water and lung vascular permeability, and reduced protein concentration in the bronchoalveolar lavage (BAL). Deficiency of alpha7 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-alpha) in the BAL with nicotine probably resulted from the suppression of NF-kappaB 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 alpha7 nAChR may provide a new therapeutic pathway for the treatment of acute lung injury.
authors: Cardiovascular Research Institute, University of California San Francisco, HSW 825, 505 Parnassus Ave., San Francisco, CA 94143-0130, USA. xiao.su@ucsf.edu
authors: Xiao
authors: X
authors: Su
authors: Jae Woo
authors: JW
authors: Lee
authors: Zachary A
authors: ZA
authors: Matthay
authors: Gabe
authors: G
authors: Mednick
authors: Tokujiro
authors: T
authors: Uchida
authors: Xiaohui
authors: X
authors: Fang
authors: Naveen
authors: N
authors: Gupta
authors: Michael A
authors: MA
authors: Matthay
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology / Q000633:toxicity; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D016207:Cytokines; D016328:NF-kappa B; D018722:Nicotinic Agonists; C498513:PNU-282987; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D002794:Choline; D006851:Hydrochloric Acid