ROSANA SOUZA BANZATO

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LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina

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  • article 5 Citação(ões) na Scopus
    Acute Lung Injury in Cholinergic-Deficient Mice Supports Anti-Inflammatory Role of alpha 7 Nicotinic Acetylcholine Receptor
    (2021) PINHEIRO, Nathalia M.; BANZATO, Rosana; TIBERIO, Iolanda; PRADO, Marco A. M.; PRADO, Vania F.; HAMOUDA, Ayman K.; PRADO, Carla M.
    (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-KDHOM) 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-1 beta) was significantly higher in VAChT-KDHOM than wild-type mice. In contrast, LPS treatment resulted in a significant increase in lung's alpha 7 nicotinic receptor level in wild-type, but not in VAChT-KDHOM mice. However, treatment with PNU 282987, a selective alpha 7 nicotinic receptor agonist, restored VAChT-KDHOM mice's ability to increase alpha 7 nicotinic receptor levels in response to LPS-induced acute lung injury and reduced lung inflammation. LPS also increased muscarinic receptors level in VAChT-KDHOM 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 alpha 7 nicotinic receptors. Pharmacological agents that increase the expression or the function of lung alpha 7 nicotinic receptors have potential clinical uses for treating acute lung injury.