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Int. J. Mol. Sci. 2017, 18(2), 403; doi:10.3390/ijms18020403

A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice

1
Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil
2
Physical Therapy Department, Hospital Sírio-Libanês, 01308-050 São Paulo, Brazil
3
Department of Bioscience, Federal University of Sao Paulo, 09972-270 Diadema, Brazil
4
Department of Biochemistry, Federal University of São Paulo, 09972-270 Diadema, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Marcello Iriti
Received: 1 December 2016 / Revised: 17 January 2017 / Accepted: 3 February 2017 / Published: 14 February 2017
(This article belongs to the Section Molecular Botany)
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Abstract

Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management. View Full-Text
Keywords: COPD; emphysema; proteinase inhibitor; EcTI COPD; emphysema; proteinase inhibitor; EcTI
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Theodoro-Júnior, O.A.; Righetti, R.F.; Almeida-Reis, R.; Martins-Oliveira, B.T.; Oliva, L.V.; Prado, C.M.; Saraiva-Romanholo, B.M.; Leick, E.A.; Pinheiro, N.M.; Lobo, Y.A.; Martins, M.A.; Oliva, M.L.V.; Tibério, I.F.L.C. A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice. Int. J. Mol. Sci. 2017, 18, 403.

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