The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCERVILHA, Daniela A. B.
dc.contributor.authorITO, Juliana T.
dc.contributor.authorLOURENCO, Juliana D.
dc.contributor.authorOLIVO, Clarice R.
dc.contributor.authorSARAIVA-ROMANHOLO, Beatriz M.
dc.contributor.authorVOLPINI, Rildo A.
dc.contributor.authorOLIVEIRA-JUNIOR, Manoel C.
dc.contributor.authorMAUAD, Thais
dc.contributor.authorMARTINS, Milton A.
dc.contributor.authorTIBERIO, Iolanda F. L. C.
dc.contributor.authorVIEIRA, Rodolfo P.
dc.contributor.authorLOPES, Fernanda D. T. Q. S.
dc.date.accessioned2019-03-26T14:31:39Z
dc.date.available2019-03-26T14:31:39Z
dc.date.issued2019
dc.description.abstractWe proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 +/- 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 mu l) or lipopolysaccharide (LPS) (1 mg/kg in 50 mu l of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-gamma, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
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.description.sponsorshipSao Paulo Research Foundation (FAPESP) [2012/15165-2]
dc.identifier.citationSCIENTIFIC REPORTS, v.9, article ID 1921, 13p, 2019
dc.identifier.doi10.1038/s41598-019-38600-z
dc.identifier.issn2045-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/31206
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUPeng
dc.relation.ispartofScientific Reports
dc.rightsopenAccesseng
dc.rights.holderCopyright NATURE PUBLISHING GROUPeng
dc.subject.otherregulatory t-cellseng
dc.subject.otherbacterial exacerbationseng
dc.subject.otherinflammatory markerseng
dc.subject.otherchronic-bronchitiseng
dc.subject.otherlungeng
dc.subject.otherexpressioneng
dc.subject.othercopdeng
dc.subject.otheremphysemaeng
dc.subject.otherseverityeng
dc.subject.otheril-10eng
dc.subject.wosMultidisciplinary Scienceseng
dc.titleThe Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Associationeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalOLIVEIRA-JUNIOR, Manoel C.:Nove Julho Univ, Lab Pulm & Exercise Immunol, Sao Paulo, Brazil
hcfmusp.author.externalVIEIRA, Rodolfo P.:Univ Brasil, Postgrad Program Bioengn & Biomed Engn, Sao Paulo, Brazil; Fed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, Brazil; Brazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, Brazil
hcfmusp.citation.scopus31
hcfmusp.contributor.author-fmusphcDANIELA APARECIDA DE BRITO CERVILHA
hcfmusp.contributor.author-fmusphcJULIANA TIYAKI ITO
hcfmusp.contributor.author-fmusphcJULIANA DIAS LOURENCO
hcfmusp.contributor.author-fmusphcCLARICE ROSA OLIVO
hcfmusp.contributor.author-fmusphcBEATRIZ MANGUEIRA SARAIVA RAMANHOLO
hcfmusp.contributor.author-fmusphcRILDO APARECIDO VOLPINI
hcfmusp.contributor.author-fmusphcTHAIS MAUAD
hcfmusp.contributor.author-fmusphcMILTON DE ARRUDA MARTINS
hcfmusp.contributor.author-fmusphcIOLANDA DE FATIMA LOPES CALVO TIBERIO
hcfmusp.contributor.author-fmusphcFERNANDA DEGOBBI TENORIO QUIRINO DOS SANTOS LOPES
hcfmusp.description.articlenumber1921
hcfmusp.description.volume9
hcfmusp.origemWOS
hcfmusp.origem.pubmed30760822
hcfmusp.origem.scopus2-s2.0-85061613947
hcfmusp.origem.wosWOS:000458571500003
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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