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

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

Author de Oliveira, Priscila Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Tanaka, Aparecida Sadae Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Batista dos Santos, Saara Maria Autor UNIFESP Google Scholar
Silva Campitelli de Barros, Bianca Carla Autor UNIFESP Google Scholar
Maza, Paloma Korehisa Autor UNIFESP Google Scholar
Puccia, Rosana Autor UNIFESP Google Scholar
Suzuki, Erika Autor UNIFESP Google Scholar
Abstract Paracoccidioides 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.
Keywords Protease-activated receptors
Epithelial cell
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES AUX PE PNPD Grant)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number FAPESP: 2011/23096-8
FAPESP: 2011/22773-6
FAPESP: 2015/25652-6
CAPES AUX PE PNPD Grant: 2386/2011
CNPq: 303357/2012-6
CNPq: 306163/2015-2
Date 2017
Published in Medical Microbiology And Immunology. New York, v. 206, n. 2, p. 149-156, 2017.
ISSN 0300-8584 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 149-156
Access rights Closed access
Type Article
Web of Science ID WOS:000398589600006

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