Fibrose pulmonar na paracoccidioidomicose: influência do fungo e do hospedeiro na fibrogênese
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Data
2017-08-03
Autores
Almeida, Débora de Fátima [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Paracoccidioidomicose (PCM) é uma micose sistêmica causada por fungos do gênero Paracoccidioides; suas principais formas clínicas são aguda/subaguda e crônica (FC). Restrita à América Latina, a PCM apresenta alta incidência no Brasil, Colômbia e Venezuela, especialmente entre os trabalhadores rurais. A maioria dos pacientes com a forma crônica da doença, mesmo após tratamento eficaz, apresentam sequelas, incluindo fibrose pulmonar (FP). Os problemas sociais, econômicos e psicológicos desencadeados pela FP são subestimados. Apesar da fibrogênese na PCM ser reconhecida como um processo precoce, seus mecanismos não estão totalmente conhecidos. Assim, o presente estudo tem por objetivo avaliar a influência de componentes dos isolados fúngicos e do hospedeiro sobre fibroblastos pulmonares. Foram utilizados fibroblastos pulmonares humanos da linhagem MRC-5 e fibroblastos pulmonares murinos, isolados de camundongos BALB/c. Fibroblastos foram cultivados in vitro com exoantígenos de isolados das espécies P. brasiliensis (Pb18 e Pb326) e P. lutzii (Pb01, Pb8334 e Pb66); gp43 purificada, e soros de pacientes com FC em diferentes momentos do tratamento (antes do tratamento, cura clínica, cura sorológica e cura aparente). Após 24 horas de cultivo, foram avaliadas a proliferação celular e produção de citocinas e fatores de crescimento por fibroblastos murinos e humanos. Nossos resultados demonstraram que componentes do fungo interferem em fibroblastos pulmonares, pela indução da proliferação, aumento dos níveis de TGF-β1 e diminuição dos níveis de IL-6 e VEGF e FGFb. Além disso, nós observamos que exoantigenos induziram altas produções de pró-colágeno I por fibroblastos humanos. Gp43 induziu aumento nos níveis de TGF-β1 em fibroblastos humanos. Em conclusão, nossos resultados demonstram pela primeira vez que componentes de P.brasiliensis e P.lutzzi interferem na fibrogênese por agir diretamente na biologia de fibroblastos pulmonares. Além disso, evidenciamos que soros de pacientes com FC interferem diferentemente na proliferação e ativação de fibroblastos pulmonares de acordo com cada momento do tratamento.
Paracoccidioidomycosis (PCM) is an endemic mycosis caused by fungi of genus Paracoccidioides; its main clinical forms are acute/subacute form and the chronic form (CF). Endemic in Latin America, PCM presents high incidence in Brazil, Colombia and Venezuela, especially among rural workers. Most part of patients with FC exhibits sequelae even after an effective fungal treatment, presenting pulmonary fibrosis (PF). The social, economic and psychological issues caused by PF are still underestimated. In PCM, fibrogenesis is recognized as an early process; however, its mechanisms are unknown. Thus, the present study aimed to evaluate the modulatory and functional influence of fungal and host components on pulmonary fibroblast. For this, it was utilized human pulmonary fibroblasts of cell line MRC-5 and murine pulmonary fibroblasts isolated of BALB/c mice. Next, cells were cultivated with different concentrations of isolates of P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334 and Pb66); purified gp43, and serum of patients with CF in different moments of treatment (before treatment, clinical cure, serological cure and apparent cure). After 24 hours, cellular proliferation and production of cytokines and grow factors by murine and human pulmonary fibroblasts were evaluated. Our results showed that the fungal components interfered in fibroblast by induce proliferation and increased levels of TGF-β1 and decreased IL-6, VEGF and bFGF. In addition we observed that exoantigens induced high production of pro-collagen I by human fibroblasts. Gp43 induced increased levels of TGF-β1 by human cells. In conclusion, our findings showed at first time that components of P.brasiliensis and P.lutzii interfere in the fibrogenesis by directly act in the biology of pulmonary fibroblast. Furthermore, we verified that serum of FC-patients interfere in proliferation and activation of pulmonary fibroblasts according to each moment of treatment.
Paracoccidioidomycosis (PCM) is an endemic mycosis caused by fungi of genus Paracoccidioides; its main clinical forms are acute/subacute form and the chronic form (CF). Endemic in Latin America, PCM presents high incidence in Brazil, Colombia and Venezuela, especially among rural workers. Most part of patients with FC exhibits sequelae even after an effective fungal treatment, presenting pulmonary fibrosis (PF). The social, economic and psychological issues caused by PF are still underestimated. In PCM, fibrogenesis is recognized as an early process; however, its mechanisms are unknown. Thus, the present study aimed to evaluate the modulatory and functional influence of fungal and host components on pulmonary fibroblast. For this, it was utilized human pulmonary fibroblasts of cell line MRC-5 and murine pulmonary fibroblasts isolated of BALB/c mice. Next, cells were cultivated with different concentrations of isolates of P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334 and Pb66); purified gp43, and serum of patients with CF in different moments of treatment (before treatment, clinical cure, serological cure and apparent cure). After 24 hours, cellular proliferation and production of cytokines and grow factors by murine and human pulmonary fibroblasts were evaluated. Our results showed that the fungal components interfered in fibroblast by induce proliferation and increased levels of TGF-β1 and decreased IL-6, VEGF and bFGF. In addition we observed that exoantigens induced high production of pro-collagen I by human fibroblasts. Gp43 induced increased levels of TGF-β1 by human cells. In conclusion, our findings showed at first time that components of P.brasiliensis and P.lutzii interfere in the fibrogenesis by directly act in the biology of pulmonary fibroblast. Furthermore, we verified that serum of FC-patients interfere in proliferation and activation of pulmonary fibroblasts according to each moment of treatment.
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Palavras-chave
Paracoccidioidomicose, Fibroblasto, Fibrose pulmonar, Paracoccidioidomycosis, Fibroblast, Pulmonary fibrosis