Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation

Pinheiro, Nathália; Miranda, Claudia; Santana, Fernanda; Bittencourt-Mernak, Márcia Isabel; Arantes-Costa, Fernanda M.; Olivo, Clarice Rosa; Perini, Adenir; Festa, Sérgio; Caperuto, Luciana C.; Tibério, Iolanda F.L.C.; Prado, Marco A. M.; Martins, Mílton A.; Prado, Vânia F.; Prado, Carla M.

doi:10.1016/j.ejphar.2020.173239

Cited by 14 publications

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“…VAChT deficient animals have a more pronounced increase in total cells and neutrophils recovered in the BALF and the levels of IL-1β. It was shown that animals with VAChT reduction have a more pronounced lung inflammatory response to diesel exhaust particles [ 40 ] and an asthma model [ 24 ]. Considering ALI, Santana et al (2021) [ 41 ] demonstrated that cytokine dysfunction observed in female VAChT-KD HOM mice increased the mortality in an ischemia and reperfusion model.…”

Section: Discussionmentioning

confidence: 99%

“…This mice model has been extensively used to evaluate cholinergic deficiency in several diseases. [17,24,37,40,41,54,55]…”

Section: Methodsmentioning

confidence: 99%

“…This mice model has been extensively used to evaluate cholinergic deficiency in several diseases. [ 17 , 24 , 37 , 40 , 41 , 54 , 55 ]. These animals were taken from the Central Vivarium of the Faculty of Medicine of the University of São Paulo, with an average weight of 20 g, approximately 6–8 weeks old.…”

Section: Methodsmentioning

confidence: 99%

“…VAChT-KD HOM mutant mice were generated as described by Prado, Martins-Silva et al (2006); they were knock-down to the VAChT gene and showed a 65% reduction in VAChT level. The content of ACh released in the synaptic cleft is directly proportional to the amount of VAChT [ 21 , 22 , 23 ], which is why VAChT-KD HOM mice have been used to study cholinergic deficiency [ 24 ]. Our group demonstrated that VAChT reduction in animals with no pathological stimulus in the lung, such as LPS or ovalbumin, caused inflammatory cell recruitment to the lung, increased pro-inflammatory cytokines release, activation of nuclear factor kappa B (NF-kB), and reduction in the activation of the Janus kinase—signal transducer and activation of the transcription—suppressor of cytokine signaling (JAK2-STAT3-SOCS3) pathway.…”

Section: Introductionmentioning

confidence: 99%

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

Pinheiro

Banzato

Tibério

et al. 2021

IJMS

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(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-1β) was significantly higher in VAChT-KDHOM 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-KDHOM mice. However, treatment with PNU 282987, a selective α7 nicotinic receptor agonist, restored VAChT-KDHOM 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-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 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.

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Section: Discussionmentioning

confidence: 99%

“…This mice model has been extensively used to evaluate cholinergic deficiency in several diseases. [17,24,37,40,41,54,55]…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Pinheiro

Banzato

Tibério

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…A remodelação do colágeno pode estar associada à presença de macrófagos tipo M2, e mostramos anteriormente que a ativação do α7nAChR pode modular o equilíbrio M1 /M2 [90]. Portanto, nossa hipótese é que essa remodelação nas fibras colágenas e elásticas pode ser atribuída aos macrófagos e a outras metaloproteases não avaliadas.…”

Section: Discussionunclassified

Papel do receptor nicotínico alfa-7 nas alterações pulmonares em modelo experimental de enfisema pulmonar induzido por elastase

Banzato¹

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The Role of the Cholinergic System in Lung Diseases

Milanković

Lazarević‐Pašti

2021

Targeting Cellular Signalling Pathways in Lung Diseases

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Effects of VAChT reduction and α7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation

Cited by 14 publications

References 58 publications

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

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

Papel do receptor nicotínico alfa-7 nas alterações pulmonares em modelo experimental de enfisema pulmonar induzido por elastase

The Role of the Cholinergic System in Lung Diseases

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