Epithelial cells treated with genistein inhibit adhesion and endocytosis of<Emphasis Type="Italic"> Paracoccidioides brasiliensis</Emphasis> |
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Authors: | J L Monteiro da Silva P F Andreotti G Benard C P Soares E T Miranda M J S Mendes-Giannini |
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Institution: | Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, 14801-902, SP, Brazil. |
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Abstract: | Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis, which although not formally considered an intracellular pathogen, can be internalized by epithelial cells in vitro and in
vivo. The mechanisms used by P. brasiliensis to adhere to and invade non-professional phagocytes have not been identified. The signal-transduction networks, involving
protein tyrosine kinase (PTK) and protein phosphatase activities, can modulate crucial events during fungal infections. In
this study, the involvement of PTK has been investigated in P. brasiliensis adherence and invasion in mammalian epithelial cells. A significant inhibition of the fungal invasion occurred after the
pre-treatment of the epithelial cells with genistein, a specific tyrosine kinase inhibitor, indicating that the tyrosine kinase
pathway is involved in P. brasiliensis internalization. In contrast, when the fungus was treated, a slight (not significant) inhibition of PTK was observed, suggesting
that PTK might not be the fungus’ transduction signal pathway during the invasion process of epithelial cells. An intense
PTK immunofluorescence labeling was observed in the periphery of the P. brasiliensis infected cells, little PTK labeling was found in both uninfected cells and yeast cells, at later infection times (8 and 24 h).
Moreover, when the epithelial cells were treated with genistein and infected with P. brasiliensis, no labeling was observed, suggesting the importance of the PTK in the infectious process. These results suggest that PTK
pathway participates in the transduction signal during the initial events of the adhesion and invasion processes of P. brasiliensis to mammalian epithelial cells. |
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Keywords: | Epithelial cells Genistein Paracoccidioides brasiliensis Protein tyrosine kinase C |
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