Long-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysema

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBANZATO, Rosana
dc.contributor.authorPINHEIRO, Nathalia M.
dc.contributor.authorOLIVO, Clarice R.
dc.contributor.authorSANTANA, Fernanda R.
dc.contributor.authorLOPES, Fernanda D. T. Q. S.
dc.contributor.authorCAPERUTO, Luciana C.
dc.contributor.authorCAMARA, Niels O.
dc.contributor.authorMARTINS, Milton A.
dc.contributor.authorTIBERIO, Iolanda F. L. C.
dc.contributor.authorPRADO, Marco Antonio M.
dc.contributor.authorPRADO, Vania F.
dc.contributor.authorPRADO, Carla M.
dc.date.accessioned2021-10-20T13:55:48Z
dc.date.available2021-10-20T13:55:48Z
dc.date.issued2021
dc.description.abstractAcetylcholine (ACh), the neurotransmitter of the cholinergic system, regulates inflammation in several diseases including pulmonary diseases. ACh is also involved in a non-neuronal mechanism that modulates the innate immune response. Because inflammation and release of pro-inflammatory cytokines are involved in pulmonary emphysema, we hypothesized that vesicular acetylcholine transport protein (VAChT) deficiency, which leads to reduction in ACh release, can modulate lung inflammation in an experimental model of emphysema. Mice with genetical reduced expression of VAChT (VAChT KDHOM 70%) and wild-type mice (WT) received nasal instillation of 50 uL of porcine pancreatic elastase (PPE) or saline on day 0. Twenty-eight days after, animals were evaluated. Elastase instilled VAChT KDHOM mice presented an increase in macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and MAC2-positive macrophages in lung tissue and peribronchovascular area that was comparable to that observed in WT mice. Conversely, elastase instilled VAChT KDHOM mice showed significantly larger number of NF-kappa B-positive cells and isoprostane staining in the peribronchovascular area when compared to elastase-instilled WT-mice. Moreover, elastase-instilled VAChT-deficient mice showed increased MCP-1 levels in the lungs. Other cytokines, extracellular matrix remodeling, alveolar enlargement, and lung function were not worse in elastase-instilled VAChT deficiency than in elastase-instilled WT-controls. These data suggest that decreased VAChT expression may contribute to the pathogenesis of emphysema, at least in part, through NF-kappa B activation, MCP-1, and oxidative stress pathways. This study highlights novel pathways involved in lung inflammation that may contribute to the development of chronic obstrutive lung disease (COPD) in cholinergic deficient individuals such as Alzheimer's disease patients.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipFundacAo de Amparo a Pesquisa do Estado de SAo PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/15817-7, 2013/02881-4, 2018/15738-9, 2018/02537-5, 2018/06088-0, 2008/55359-5]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [303035/2018-8]
dc.description.sponsorshipInstituto dos Laboratorios de InvestigacAo Medica do Hospital das Clinicas da Faculdade de Medicina da Universidade de SAo Paulo, Brazil [LIM-20-HC/FMUSP]
dc.identifier.citationSCIENTIFIC REPORTS, v.11, n.1, article ID 15918, 13p, 2021
dc.identifier.doi10.1038/s41598-021-95211-3
dc.identifier.issn2045-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/42043
dc.language.isoeng
dc.publisherNATURE PORTFOLIOeng
dc.relation.ispartofScientific Reports
dc.rightsopenAccesseng
dc.rights.holderCopyright NATURE PORTFOLIOeng
dc.subject.othernonneuronal cholinergic systemeng
dc.subject.otherfactor-kappa-beng
dc.subject.otherrespiratory mechanicseng
dc.subject.otherlungeng
dc.subject.otherdiseaseeng
dc.subject.otherpathogenesiseng
dc.subject.othernerveeng
dc.subject.othermiceeng
dc.subject.othertransportereng
dc.subject.othermacrophageeng
dc.subject.wosMultidisciplinary Scienceseng
dc.titleLong-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysemaeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalPINHEIRO, Nathalia M.:Univ Fed Sao Paulo, Dept Biosci, Rua Silva Jardim 136, Santos, SP, Brazil
hcfmusp.author.externalSANTANA, Fernanda R.:Univ Fed Sao Paulo, Dept Med Nephrol, Sao Paulo, Brazil; Univ Fed Sao Paulo, Dept Biol Sci, Diadema, Brazil
hcfmusp.author.externalCAPERUTO, Luciana C.:Univ Fed Sao Paulo, Dept Biol Sci, Diadema, Brazil
hcfmusp.author.externalCAMARA, Niels O.:Univ Sao Paulo, Immunol, Sao Paulo, Brazil
hcfmusp.author.externalPRADO, Marco Antonio M.:Robarts Res Inst, Mol Med Grp, London, ON, Canada; Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada; Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada
hcfmusp.author.externalPRADO, Vania F.:Robarts Res Inst, Mol Med Grp, London, ON, Canada; Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada; Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcROSANA SOUZA BANZATO
hcfmusp.contributor.author-fmusphcCLARICE ROSA OLIVO
hcfmusp.contributor.author-fmusphcFERNANDA DEGOBBI TENORIO QUIRINO DOS SANTOS LOPES
hcfmusp.contributor.author-fmusphcMILTON DE ARRUDA MARTINS
hcfmusp.contributor.author-fmusphcIOLANDA DE FATIMA LOPES CALVO TIBERIO
hcfmusp.contributor.author-fmusphcCARLA MAXIMO PRADO
hcfmusp.description.articlenumber15918
hcfmusp.description.issue1
hcfmusp.description.volume11
hcfmusp.origemWOS
hcfmusp.origem.pubmed34354132
hcfmusp.origem.scopus2-s2.0-85112004253
hcfmusp.origem.wosWOS:000684434700033
hcfmusp.publisher.cityBERLINeng
hcfmusp.publisher.countryGERMANYeng
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