rBmTI-6 attenuates pathophysiological and inflammatory parameters of induced emphysema in mice

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art_DURAN_rBmTI6_attenuates_pathophysiological_and_inflammatory_parameters_of_induced_2018.PDF (1.45 MB)
Citações na Scopus
6
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
DURAN, Adriana Feliciano Alves
NEVES, Luana de Paiva
SILVA, Flavia Ribeiro Santos da
MACHADO, Gabriel Capella
FERREIRA, Graziele Cristina
TANAKA, Aparecida Sadae
SASAKI, Sergio Daishi
Citação
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, v.111, p.1214-1221, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Protease/anti-protease imbalance is the main pathogenic mechanism of emphysema and protease inhibitors have been recognized as potential molecules to treat the disease conditions. In this work the rBmTI-6 first domain (rBmTI-6-D1), a recombinant Kunitz-type serine proteinase inhibitor, was used to verify its effect in prevention or minimization of PPE-induced emphysema in mice. C57BL/6 mice were submitted to a PPE-induced emphysema model and treated with rBmTI-6-D1 before the emphysema development. We showed that the rBmTI-6D1 treatment was sufficient to avoid the loss of elastic recoil, an effective decrease in alveolar enlargement and in the number of macrophages and lymphocytes in bronchoalveolar lavage fluid. Proteolytic analysis showed a significant increase in elastase activity in PPE-VE (induced emphysema) group that is controlled by rBmTI-6D1. Kallikrein activity was decreased in the PPE-rBmTI6 (induced emphysema and inhibitor treated) group when compared to PPE-VE group. Although rBmTI-6-D1, did not present a neutrophil elastase (NE) inhibitory activity, the results show that the inhibitor interfered in the pathway of NE secretion in PPE-emphysema mice model. The role of rBmTI-6-D1 in the prevention of emphysema development in the mice model, apparently, is related with a control of inflammatory response due the trypsin/kallikrein inhibitory activity of rBmTI-6-D1.
Palavras-chave
COPD, Emphysema, Serine protease inhibitor, rBmTI-6
URI
https://observatorio.fm.usp.br/handle/OPI/28001
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/20
Artigos e Materiais de Revistas Científicas - ODS/03