Alpha-7 nicotinic receptor agonist protects mice against pulmonary emphysema induced by elastase

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dc.citation.volume47
dc.contributor.authorBanzato, Rosana
dc.contributor.authorPinheiro-Menegasso, Nathalia Montouro [UNIFESP]
dc.contributor.authorSantana, Fernanda Paula Roncon [UNIFESP]
dc.contributor.authorOlivo, Clarice Rosa
dc.contributor.authorTaguchi, Laura [UNIFESP]
dc.contributor.authorSantos, Stheffany de Oliveira [UNIFESP]
dc.contributor.authorFukuzaki, Silvia
dc.contributor.authorTeodoro, Walcy Paganelli Rosolia
dc.contributor.authorLopes, Fernanda Degobbi Tenorio Quirino dos Santos
dc.contributor.authorTibério, Iolanda de Fátima Lopes Calvo
dc.contributor.authorToledo-Arruda, Alessandra Choqueta de
dc.contributor.authorPrado, Marco Antônio Máximo
dc.contributor.authorPrado, Vania Ferreira
dc.contributor.authorPrado , Carla Máximo [UNIFESP]
dc.contributor.authorLatteshttp://lattes.cnpq.br/9600880359624334
dc.contributor.authorLatteshttp://lattes.cnpq.br/8960401765088965
dc.contributor.authorLatteshttp://lattes.cnpq.br/0335008572194595
dc.contributor.authorLatteshttp://lattes.cnpq.br/0090429486050126
dc.contributor.authorLatteshttp://lattes.cnpq.br/4409788652533408
dc.contributor.authorLatteshttp://lattes.cnpq.br/1848955229237487
dc.contributor.authorLatteshttp://lattes.cnpq.br/0720259963845051
dc.contributor.authorLatteshttp://lattes.cnpq.br/2069814538238357
dc.contributor.authorLatteshttp://lattes.cnpq.br/7240963502716211
dc.contributor.authorLatteshttp://lattes.cnpq.br/8148205870336524
dc.contributor.authorLatteshttp://lattes.cnpq.br/2961494666434143
dc.contributor.authorLatteshttp://lattes.cnpq.br/8706664565242249
dc.contributor.authorLatteshttp://lattes.cnpq.br/3222014752923501
dc.contributor.authorLatteshttp://lattes.cnpq.br/1740478426977844
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2024-07-03T22:11:18Z
dc.date.available2024-07-03T22:11:18Z
dc.date.issued2024-06-01
dc.description.abstractPulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50 µl, 0.667 IU) to induce emphysema. Treatment with PNU-282987 (2.0 mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 08/55359-5
dc.description.sponsorshipIDFAPESP: 14/25689-4
dc.description.sponsorshipIDFAPESP: 20/13480-4
dc.description.sponsorshipIDFAPESP: 18/15738-9
dc.description.sponsorshipIDCNPq: 306278/2015-4
dc.format.extent958-974
dc.identifierhttps://pubmed.ncbi.nlm.nih.gov/38227123/
dc.identifier.citationBANZATO, Rosana, PINHEIRO-MENEGASSO, Nathalia Montouro, SANTANA NOVELLI, Fernanda Paula Roncon et al. Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase. Inflammation 47, 958–974 (2024). https://doi.org/10.1007/s10753-023-01953-9
dc.identifier.doi10.1007/s10753-023-01953-9
dc.identifier.issn1573-2576
dc.identifier.urihttps://hdl.handle.net/11600/71341
dc.languageeng
dc.publisherSpringer Nature
dc.relation.ispartofInflammation
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectPNU282987
dc.subjectAcetylcholine
dc.subjectAlpha-7 nicotinic acetylcholine receptor
dc.subjectAnimal models
dc.subjectInflammation
dc.subjectPulmonary emphysema
dc.titleAlpha-7 nicotinic receptor agonist protects mice against pulmonary emphysema induced by elastase
dc.typeinfo:eu-repo/semantics/article
unifesp.campusInstituto de Saúde e Sociedade (ISS)
unifesp.departamentoBiociências
unifesp.graduateProgramInterdisciplinar em Ciências da Saúde
unifesp.knowledgeAreaOutra
unifesp.researchAreaMediadores da Inflamação Pulmonar
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