Acute Lung Injury in Cholinergic-Deficient Mice Supports Anti-Inflammatory Role of α7 Nicotinic Acetylcholine Receptor

International Journal of Molecular Sciences

Ayman K. Hamouda¹  Nathalia M. Pinheiro²  Carla M. Prado²  Rosana Banzato³  Iolanda Tibério³  Vânia F. Prado³  Marco A. M. Prado⁴ 

[1] College of Pharmacy, University of Texas at Tyler, Tyler, TX 75799, USA;Department of Bioscience, Federal University of Sao Paulo, Santos 11015-020, SP, Brazil;Department of Medicine, School of Medicine, University of Sao Paulo, Sao Paulo 01246-903, SP, Brazil;Molecular Medicine Group, Robarts Research Institute, London, ON N6A 5B7, Canada;

关键词: nicotinic acetylcholine receptors;    muscarinic acetylcholine receptors;    acute lung injury;    PNU 282987;    cholinergic anti-inflammatory pathway;   

DOI  :  10.3390/ijms22147552

来源: DOAJ

【 摘 要 】

(1) Background: The lung cholinergic pathway is important for controlling pulmonary inflammation in acute lung injury, a condition that is characterized by a sudden onset and intense inflammation. This study investigated changes in the expression levels of nicotinic and muscarinic acetylcholine receptors (nAChR and mAChR) in the lung during acute lung injury. (2) Methods: acute lung injury (ALI) was induced in wild-type and cholinergic-deficient (VAChT-KD^HOM) mice using intratracheal lipopolysaccharide (LPS) instillation with or without concurrent treatment with nicotinic ligands. Bronchoalveolar lavage fluid was collected to evaluate markers of inflammation, and then the lung was removed and processed for isolation of membrane fraction and determination of acetylcholine receptors level using radioligand binding assays. (3) Results: LPS-induced increase in lung inflammatory markers (e.g., neutrophils and IL-1β) was significantly higher in VAChT-KD^HOM than wild-type mice. In contrast, LPS treatment resulted in a significant increase in lung’s α7 nicotinic receptor level in wild-type, but not in VAChT-KD^HOM mice. However, treatment with PNU 282987, a selective α7 nicotinic receptor agonist, restored VAChT-KD^HOM mice’s ability to increase α7 nicotinic receptor levels in response to LPS-induced acute lung injury and reduced lung inflammation. LPS also increased muscarinic receptors level in VAChT-KD^HOM mice, and PNU 282987 treatment reduced this response. (4) Conclusions: Our data indicate that the anti-inflammatory effects of the lung cholinergic system involve an increase in the level of α7 nicotinic receptors. Pharmacological agents that increase the expression or the function of lung α7 nicotinic receptors have potential clinical uses for treating acute lung injury.

【 授权许可】

Unknown