Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner

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dc.citation.issue2
dc.citation.volume206
dc.contributor.authorde Oliveira, Priscila [UNIFESP]
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorTanaka, Aparecida Sadae [UNIFESP]
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.authorBatista dos Santos, Saara Maria [UNIFESP]
dc.contributor.authorSilva Campitelli de Barros, Bianca Carla [UNIFESP]
dc.contributor.authorMaza, Paloma Korehisa [UNIFESP]
dc.contributor.authorPuccia, Rosana [UNIFESP]
dc.contributor.authorSuzuki, Erika [UNIFESP]
dc.coverageNew York
dc.date.accessioned2020-07-17T14:02:34Z
dc.date.available2020-07-17T14:02:34Z
dc.date.issued2017
dc.description.abstractParacoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549. Cytokine secretion was reduced by antagonistic peptides for PAR-1 and PAR-2, but not for PAR-4. P. brasiliensis proteases were isolated from fungal culture supernatants in a p-aminomethylbenzamidine-Sepharose column. The obtained fractions were tested for enzymatic activity against fluorescence resonance energy transfer (FRET) peptides derived from sequences that spanned the activation sites of human PARs. The eluted fraction, termed PbP, contained protease activities that were able to hydrolyze the FRET peptides. PbP also induced IL-6 and IL-8 secretion in A549 epithelial cells, which was reduced upon heat inactivation of PbP, incubation with antagonistic peptides for PAR-1 and PAR-2, and the protease inhibitors aprotinin, leupeptin, and E-64. Together, these results show for the first time that P. brasiliensis yeasts secrete proteases that activate PARs in lung epithelial cells, leading to cytokine secretion.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Rua Botucatu,862 Ed Antonio CM Paiva 6 Andar, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Rua Tres Maio,100 INFAR 1 Andar, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Rua Tres Maio,100 INFAR 5 Andar, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Rua Pedro Toledo,699 7 Andar, BR-04039032 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Rua Botucatu,862 Ed Antonio CM Paiva 8 Andar, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Rua Botucatu,862 Ed Antonio CM Paiva 6 Andar, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Rua Tres Maio,100 INFAR 1 Andar, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Rua Tres Maio,100 INFAR 5 Andar, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biophys, Escola Paulista Med, Rua Pedro Toledo,699 7 Andar, BR-04039032 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Rua Botucatu,862 Ed Antonio CM Paiva 8 Andar, BR-04023062 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES AUX PE PNPD Grant)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipIDFAPESP: 2011/23096-8
dc.description.sponsorshipIDFAPESP: 2011/22773-6
dc.description.sponsorshipIDFAPESP: 2015/25652-6
dc.description.sponsorshipIDCAPES AUX PE PNPD Grant: 2386/2011
dc.description.sponsorshipIDCNPq: 303357/2012-6
dc.description.sponsorshipIDCNPq: 306163/2015-2
dc.format.extent149-156
dc.identifierhttp://dx.doi.org/10.1007/s00430-016-0490-x
dc.identifier.citationMedical Microbiology And Immunology. New York, v. 206, n. 2, p. 149-156, 2017.
dc.identifier.doi10.1007/s00430-016-0490-x
dc.identifier.issn0300-8584
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54872
dc.identifier.wosWOS:000398589600006
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofMedical Microbiology And Immunology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectProtease-activated receptorsen
dc.subjectEpithelial cellen
dc.subjectFungusen
dc.subjectParacoccidioidesen
dc.subjectProteaseen
dc.subjectCytokineen
dc.titleParacoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manneren
dc.typeinfo:eu-repo/semantics/article
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