ArticleMedical microbiology and immunology2017
Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner.
Article in Medical microbiology and immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 11 citations in OpenAlex.
- PAR2-β-arrestin 2-ERK axis mediatesiScience · 2026Article
- IL-6 Degradation by Secreted Proteases FromInternational journal of microbiology · 2025Article
- Article
- More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans.Journal of fungi (Basel, Switzerland) · 2023Review
- Human Airway Epithelium Responses to Invasive Fungal Infections: A Critical Partner in Innate Immunity.Journal of fungi (Basel, Switzerland) · 2022Review
- Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections.Journal of fungi (Basel, Switzerland) · 2022Review
- Updates inJournal of fungi (Basel, Switzerland) · 2021Review
- Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts.Memorias do Instituto Oswaldo Cruz · 2021Article
- Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner.Scientific reports · 2020Article
- Paracoccidioides species present distinct fungal adherence to epithelial lung cells and promote different IL-8 secretion levels.Medical microbiology and immunology · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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