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

• Published in: International journal of molecular sciences 2017-02, Vol.18 (2), p.403-403
• Main Authors: Theodoro-Júnior, Osmar Aparecido, Righetti, Renato Fraga, Almeida-Reis, Rafael, Martins-Oliveira, Bruno Tadeu, Oliva, Leandro Vilela, Prado, Carla Máximo, Saraiva-Romanholo, Beatriz Mangueira, Leick, Edna Aparecida, Pinheiro, Nathalia Montouro, Lobo, Yara Aparecida, Martins, Mílton de Arruda, Oliva, Maria Luiza Vilela, Tibério, Iolanda de Fátima Lopes Calvo
• Format: Article
• Language: English
• Subjects: Airway Remodeling - drug effects; Alveoli; Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchus; Chronic obstructive pulmonary disease; Collagen; Disease Models, Animal; Elastase; Emphysema; Extracellular Matrix - metabolism; Fabaceae - chemistry; Gelatinase B; Inflammation; Leukocytes; Lung diseases; Male; Matrix metalloproteinase; Metalloproteinase; Mice; Morphometry; Mucins - biosynthesis; Nitric oxide; Nitric-oxide synthase; Obstructive lung disease; Oxidative Stress; Pancreatic Elastase - metabolism; Plant Extracts - pharmacology; Pneumonia - drug therapy; Pneumonia - metabolism; Pneumonia - pathology; Pneumonia - physiopathology; Protease Inhibitors - pharmacology; Proteinase; Proteinase inhibitors; Respiratory system; Rodents; Tissue inhibitor of metalloproteinase 1; Trypsin; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18020403

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, 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.