A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress

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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.authorVASCONCELOS, Luiz Henrique Cesar
dc.contributor.authorSILVA, Maria da Conceicao Correia
dc.contributor.authorCOSTA, Alana Cristina
dc.contributor.authorOLIVEIRA, Giuliana Amanda de
dc.contributor.authorSOUZA, Iara Leao Luna de
dc.contributor.authorQUEIROGA, Fernando Ramos
dc.contributor.authorARAUJO, Layanne da Cunha
dc.contributor.authorCARDOSO, Glebia Alexa
dc.contributor.authorRIGHETTI, Renato Fraga
dc.contributor.authorSILVA, Alexandre Sergio
dc.contributor.authorSILVA, Patricia Mirella da
dc.contributor.authorCARVALHO, Carla Roberta de Oliveira
dc.contributor.authorVIEIRA, Giciane Carvalho
dc.contributor.authorTIBERIO, Iolanda de Fatima Lopes Calvo
dc.contributor.authorCAVALCANTE, Fabiana de Andrade
dc.contributor.authorSILVA, Bagnolia Araujo da
dc.date.accessioned2019-02-21T17:28:10Z
dc.date.available2019-02-21T17:28:10Z
dc.date.issued2019
dc.description.abstractAsthma is a heterogeneous disease of the airways characterized by chronic inflammation associated with bronchial and smooth muscle hyperresponsiveness. Currently, different murine models for the study of asthma show poor bronchial hyperresponsiveness due to a scarcity of smooth muscle and large airways, resulting in a failure to reproduce smooth muscle hyperreactivity. Thus, we aimed to standardize a guinea pig model of chronic allergic lung inflammation mimicking airway smooth muscle hyperreactivity observed in asthmatics (Asth). Animals were randomly divided into a control group (Ctrl), which received saline (0.9% NaCl), and the Asth group, subjected to in vivo sensitization with ovalbumin (OVA) nebulization. Morphological analysis was performed by hematoxylin-eosin staining. Bronchial hyperresponsiveness was evaluated by nebulization time in the fifth, sixth, and seventh inhalations (NT5-7) and tracheal isometric contractions were assessed by force transducer. Total antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and protein expression by Western blot. Histologically, the Asth group developed peribronchial cellular infiltrate, epithelial hyperplasia and smooth muscle thickening. After the fourth nebulization, the Asth group developed bronchial hyperreactivity. The trachea from the Asth group contracted after in vitro stimulation with OVA, differing from the Ctrl group, which showed no response. Additionally, airway smooth muscle hyperreactivity to carbachol and histamine was observed in the Asth group only in intact epithelium preparations, but not to KCl, and this effect was associated with an augmented production of reactive oxygen species. Moreover, lung inflammation impaired the relaxant potency of isoproterenol only in intact epithelium preparations, without interfering with nifedipine, and it was found to be produced by transforming growth factor-beta negative modulation of beta adrenergic receptors and, furthermore, big-conductance Ca2+-sensitive K+ channels. These effects were also associated with increased levels of phosphatidylinositol 3-kinases but not extracellular signal-regulated kinases 1/2 or phosphorylation, and augmented alpha-actin content as well, explaining the increased smooth muscle mass. Furthermore, pulmonary antioxidant capacity was impaired in the Asth group. Therefore, we developed a standardized and easy-touse, reproducible guinea pig model of lung inflammation that mimics airway smooth muscle hypercontractility, facilitating the investigation of the mechanisms of bronchial hyperresponsiveness in asthma and new therapeutic alternatives.eng
dc.description.indexPubMedeng
dc.description.sponsorshipCAPES
dc.description.sponsorshipCNPq
dc.identifier.citationFRONTIERS IN PHARMACOLOGY, v.9, article ID 1547, 15p, 2019
dc.identifier.doi10.3389/fphar.2018.01547
dc.identifier.issn1663-9812
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/30921
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Pharmacology
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectairwayseng
dc.subjectasthmaeng
dc.subjectcontractile reactivityeng
dc.subjectrelaxationeng
dc.subjectoxidative stresseng
dc.subject.othergrowth-factor-betaeng
dc.subject.otherin-vitro modeleng
dc.subject.othertissue mechanicseng
dc.subject.otherhuman trachealeng
dc.subject.otherasthmaeng
dc.subject.othercontractioneng
dc.subject.otherhyperresponsivenesseng
dc.subject.otherpharmacologyeng
dc.subject.otherresponsivenesseng
dc.subject.otherproliferationeng
dc.subject.wosPharmacology & Pharmacyeng
dc.titleA Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stresseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalVASCONCELOS, Luiz Henrique Cesar:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalSILVA, Maria da Conceicao Correia:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalCOSTA, Alana Cristina:Univ Fed Paraiba, Ctr Ciencias Saude, Dept Ciencias Farmaceut, Grad Farm, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalOLIVEIRA, Giuliana Amanda de:Univ Fed Paraiba, Ctr Ciencias Saude, Dept Ciencias Farmaceut, Grad Farm, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalSOUZA, Iara Leao Luna de:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalQUEIROGA, Fernando Ramos:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalARAUJO, Layanne da Cunha:Univ Sao Paulo, Inst Ciencias Biol, Programa Posgrad Ciencias Fisiol Humana, Sao Paulo, Brazil
hcfmusp.author.externalCARDOSO, Glebia Alexa:Univ Fed Paraiba, Programa Associado Posgrad Educ Fis, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalSILVA, Alexandre Sergio:Univ Fed Paraiba, Programa Associado Posgrad Educ Fis, Joao Pessoa, Paraiba, Brazil; Hosp Sirio Libanes, Sao Paulo, Brazil
hcfmusp.author.externalSILVA, Patricia Mirella da:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil; Univ Fed Paraiba, Ctr Ciencias Saude, Dept Educ Fis, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalCARVALHO, Carla Roberta de Oliveira:Univ Sao Paulo, Inst Ciencias Biol, Programa Posgrad Ciencias Fisiol Humana, Sao Paulo, Brazil; Univ Fed Paraiba, Ctr Ciencias Saude, Dept Biol Mol, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalVIEIRA, Giciane Carvalho:Univ Sao Paulo, Inst Ciencias Biol, Dept Biofis & Fisiol, Sao Paulo, Brazil
hcfmusp.author.externalCAVALCANTE, Fabiana de Andrade:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil; Univ Fed Paraiba, Ctr Ciencias Saude, Dept Fisiol & Patol, Joao Pessoa, Paraiba, Brazil
hcfmusp.author.externalSILVA, Bagnolia Araujo da:Univ Fed Paraiba, Ctr Ciencias Saude, Programa Posgrad Prod Nat & Sintet Bioat, Joao Pessoa, Paraiba, Brazil; Univ Fed Paraiba, Ctr Ciencias Saude, Dept Ciencias Farmaceut, Joao Pessoa, Paraiba, Brazil
hcfmusp.citation.scopus10
hcfmusp.contributor.author-fmusphcRENATO FRAGA RIGHETTI
hcfmusp.contributor.author-fmusphcIOLANDA DE FATIMA LOPES CALVO TIBERIO
hcfmusp.description.articlenumber1547
hcfmusp.description.volume9
hcfmusp.origemWOS
hcfmusp.origem.pubmed30814952
hcfmusp.origem.scopus2-s2.0-85065472444
hcfmusp.origem.wosWOS:000456733500001
hcfmusp.publisher.cityLAUSANNEeng
hcfmusp.publisher.countrySWITZERLANDeng
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