A plant proteinase inhibitor from Enterolobium contortisiliquum attenuates airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma
Adriana Palmeira Dias Rodrigues1, Anelize Sartori Santos Bortolozzo1, Fernanda Magalhães Arantes-Costa1, Beatriz Mangueira Saraiva-Romanholo1,2, Flávia Castro Ribas de Souza1, Thayse Regina Brüggemann1, Fernanda Paula Roncon Santana1, Marlon Vilela de Brito3, Camila Ramalho Bonturi3, Natalia Neto dos Santos Nunes3, Carla Máximo Prado4, Edna Aparecida Leick1, Maria Luiza Vilela Oliva3, Milton de Arruda Martins1, Renato Fraga Righetti1,5 and Iolanda de Fátima Lopes Calvo Tibério1
1Faculdade de Medicina FMUSP, Universidade de São Paulo, Department of Clinical Medicine, 2University City of São Paulo (UNICID), 3University Federal of São Paulo, Department of Biochemistry, São Paulo, 4Department of Bioscience, Federal University of São Paulo, Santos and 5Hospital Sírio-Libanês, Departamento de Reabilitação, São Paulo, Brazil
Offprint requests to: Iolanda de Fátima Lopes Calvo Tibério, M.D.PhD, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 - Sala 1210 - 01246-903 - São Paulo - SP – Brazil. e-mail: iocalvo@uol.com.br
Summary. Introduction. Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for asthma. Purpose. The aim of the present study was to evaluate the effects of Enterolobium contortisiliquum trypsin inhibitor (EcTI) on pulmonary mechanical function, eosinophilic recruitment, inflammatory cytokines, remodeling and oxidative stress in an experimental model of chronic allergic pulmonary inflammation. Methods. BALB/c mice were divided into 4 groups: C (saline i.p and inhalations with saline), OVA (ovalbumin i.p and inhalations with ovalbumin); C+EC (saline i.p, inhalations with s aline and treatment with EcTI); OVA+EC (ovalbumin i.p, inhalations with ovalbumin and treatment with EcTI). On day 29, we performed the following tests: resistance (Rrs) and elastance (Ers) of the respiratory system; (b) quantify eosinophils, 8-ISO-PGF2α, collagen and elastic fiber volume fractions; (c) IFN-γ, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-β, iNOS and p65-NFκB-positive cells in the airway and alveolar walls. Results. In OVA+EC group, there was an attenuation of the Rrs and Ers, reduction of eosinophils, IL-4, IL-5, IL-13, IFN-γ, iNOS and p65-NF κB-positive cells compared to OVA group. The 8-ISO-PGF2α, elastic and collagen fibers volume fractions as well as the positive cells for MMP-9, TIMP-1 and TGF-β positive cells were decreased in OVA+EC compared to the OVA group. Conclusion. EcTI attenuates bronchial hyperresponsiveness, inflammation, remodeling and oxidative stress activation in this experimental mouse model of asthma. Histol Histopathol 34, 537-552 (2019)
Key words: Asthma, Pulmonary inflammation, Plant proteinase inhibitor, Enterolobium contortisiliquum Trypsin Inhibitor
DOI: 10.14670/HH-18-059