Acute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profile

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dc.citation.issue1
dc.citation.volume31
dc.contributor.authorPinheiro, Nathalia Montouro
dc.contributor.authorSantana, Fernanda Paula Roncon [UNIFESP]
dc.contributor.authorAlmeida, Rafael Ribeiro
dc.contributor.authorGuerreiro, Marina [UNIFESP]
dc.contributor.authorMartins, Milton de Arruda
dc.contributor.authorCaperuto, Luciana Chagas [UNIFESP]
dc.contributor.authorCâmara, Niels Olsen Saraiva
dc.contributor.authorWensing, Lislaine Andrade
dc.contributor.authorPrado, Vânia Ferreira
dc.contributor.authorTibério, Iolanda de Fátima Lopes Calvo
dc.contributor.authorPrado, Marco Antônio Máximo
dc.contributor.authorPrado, Carla Maximo [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageBethesda
dc.date.accessioned2020-07-31T12:46:58Z
dc.date.available2020-07-31T12:46:58Z
dc.date.issued2017
dc.description.abstractNicotinic alpha-7 acetylcholine receptor (nAChR alpha 7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of alpha 7nAChR as a therapeutic target, we evaluated whether PNU-282987, an alpha 7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL1 beta, TNF-alpha, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P<0.05). In addition, lung NF-kappa B phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9(+) and -2(+) cells, whereas the number of tissue inhibitor of metalloproteinase-1(+) cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, anagonist of alpha 7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on alpha 7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Camara, N. O. S., Wensing, L. A., Prado, V. F., Tiberio, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profile.en
dc.description.affiliationUniv Sao Paulo, Dept Med, Sch Med, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biol Sci, Diadema, Brazil
dc.description.affiliationUniv Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada
dc.description.affiliationUniv Western Ontario, Dept Anat & Cell Biol, London, ON, Canada
dc.description.affiliationUniv Fed Sao Paulo, Dept Biosci, Santos, Brazil
dc.description.affiliationUnifespDepartment of Biological Science, Universidade Federal de São Paulo, Diadema, Brazil
dc.description.affiliationUnifespDepartment of Bioscience, Universidade Federal de São Paulo (UNIFESP), Rua Silva Jardim, 136 Vila Mathias, Santos SP, Brazil, 11015-020
dc.description.sourceWeb of Science
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: 2008/55359-5
dc.description.sponsorshipIDFAPESP: 2012/02270-2
dc.description.sponsorshipIDFAPESP: 2013/02881-4
dc.description.sponsorshipIDFAPESP: 2014/25689-4
dc.description.sponsorshipIDCNPq: 471224/2009-0
dc.description.sponsorshipIDCNPq: 476877/2012-1
dc.description.sponsorshipIDCNPq: 304465/2012-7
dc.format.extent320-332
dc.identifierhttps://dx.doi.org/10.1096/fj.201600431R
dc.identifier.citationFaseb Journal. Bethesda, v. 31, n. 1, p. 320-332, 2017.
dc.identifier.doi10.1096/fj.201600431R
dc.identifier.issn0892-6638
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56484
dc.identifier.wosWOS:000392177600030
dc.language.isoeng
dc.publisherFederation Amer Soc Exp Biol
dc.relation.ispartofFaseb Journal
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAcetylcholine experimental modelen
dc.subjectARDSen
dc.subjectLung inflammationen
dc.subjectNicotine receptoren
dc.subjectNicotinic agonisten
dc.titleAcute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profileen
dc.typeinfo:eu-repo/semantics/article
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