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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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
Total Authors: 9
Document type: Journal article
Source: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 206, n. 2, p. 149-156, APR 2017.
Web of Science Citations: 2

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)

FAPESP's process: 11/23096-8 - Importance of proteases of Paracoccidioides Brasiliensis in host immune response
Grantee:Priscila de Oliveira Colombo
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 11/22773-6 - Studies of the mechanisms of adhesion and cytokine modulation during interaction of epithelial cells and pathogenic fungi
Grantee:Erika Suzuki de Toledo
Support Opportunities: Regular Research Grants
FAPESP's process: 15/25652-6 - Study of the communication between receptors, and their signaling pathways, in fungus-induced cytokine secretion in epithelial cells
Grantee:Erika Suzuki de Toledo
Support Opportunities: Regular Research Grants