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

Autor(es)

Alves Duran, Adriana Feliciano ^[1] ; Neves, Luana de Paiva ^[1] ; Santos da Silva, Flavia Ribeiro ^[1] ; Machado, Gabriel Capella ^[1] ; Ferreira, Graziele Cristina ^[1] ; Lourenco, Juliana D. ^[2] ; Tanaka, Aparecida Sadae ^[3] ; Martins, Milton de Arruda ^[2] ; Lopes, Fernanda D. T. Q. S. ^[2] ; Sasaki, Sergio Daishi ^[1]

Afiliação do(s) autor(es)

^[1] UFABC, CCNH, Campus Sao Bernardo Campo Rua Arcturus 03, BR-09606070 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Med, Sao Paulo - Brazil

^[3] UNIFESP EPM, Dept Bioquim, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 111, p. 1214-1221, MAY 2018.
• Citações Web of Science: 1

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. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 11/07001-7 - Estudos da atividade de inibidores de serinoproteases originários do carrapato Rhipicephalus Boophilus microplus em modelo de enfisema pulmonar em camundongos e caracterização molecular das atividades de serinoproteases presentes no modelo
• Beneficiário: Sergio Daishi Sasaki
• Modalidade de apoio: Auxílio à Pesquisa - Regular