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

Autor(es)

de Oliveira, Priscila ; Juliano, Maria Aparecida ; Tanaka, Aparecida Sadae ; Carmona, Adriana Karaoglanovic ; Batista dos Santos, Saara Maria ; Silva Campitelli de Barros, Bianca Carla ; Maza, Paloma Korehisa ; Puccia, Rosana ; Suzuki, Erika

• Tipo de documento: Artigo Científico
• Fonte: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 206, n. 2, p. 149-156, APR 2017.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 11/23096-8 - Importância de proteases de Paracoccidioides Brasiliensis na resposta imune do hospedeiro
• Beneficiário: Priscila de Oliveira Colombo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/22773-6 - Estudos sobre os mecanismos de adesão e modulação de citocinas durante a interação entre células epiteliais e fungos patogênicos
• Beneficiário: Erika Suzuki de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/25652-6 - Estudo da comunicação entre receptores e suas vias de sinalização na secreção de citocinas, induzida por fungos em células epiteliais
• Beneficiário: Erika Suzuki de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular