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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Acute Lung Injury in Cholinergic-Deficient Mice Supports Anti-Inflammatory Role of alpha 7 Nicotinic Acetylcholine Receptor

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Autor(es):
Pinheiro, Nathalia M. [1, 2] ; Banzato, Rosana [3] ; Tiberio, Iolanda [3] ; Prado, Marco A. M. [4, 5, 6] ; Prado, Vania F. [3, 6] ; Hamouda, Ayman K. [2] ; Prado, Carla M. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biosci, BR-11015020 Santos, SP - Brazil
[2] Univ Texas Tyler, Coll Pharm, Tyler, TX 75799 - USA
[3] Univ Sao Paulo, Sch Med, Dept Med, BR-01246903 Sao Paulo, SP - Brazil
[4] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5B7 - Canada
[5] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5B7 - Canada
[6] Robarts Res Inst, Mol Med Grp, London, ON N6A 5B7 - Canada
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 14 JUL 2021.
Citações Web of Science: 0
Resumo

(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. (AU)

Processo FAPESP: 18/15738-9 - Efeito do sistema colinérgico anti-inflamatório e dos receptores nicotínicos em modelo murino de lesão pulmonar aguda induzida por LPS
Beneficiário:Nathalia Montouro Pinheiro Menegasso
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 20/13480-4 - Screening virtual e avaliação in vitro e in vivo dos receptores nicotínicos como alvo terapêutico para SARS-CoV-2: enfoque na interação com a ECA2.
Beneficiário:Carla Máximo Prado
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 19/15665-4 - Efeito do sistema colinérgico anti-inflamatório e dos receptores nicotínicos em modelo murino de lesão pulmonar aguda induzida por LPS
Beneficiário:Nathalia Montouro Pinheiro Menegasso
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado