The Plant Proteinase Inhibitor CrataBL Plays a Role in Controlling Asthma Response in Mice

Author:

Bortolozzo Anelize Sartori Santos1,Rodrigues Adriana Palmeira Dias1,Arantes-Costa Fernanda Magalhães1ORCID,Saraiva-Romanholo Beatriz Mangueira12,Souza Flávia Castro Ribas de1ORCID,Brüggemann Thayse Regina1,Brito Marlon Vilela de3,Ferreira Rodrigo da Silva4,Correia Maria Tereza dos Santos5ORCID,Paiva Patrícia Maria Guedes5,Prado Carla Máximo6ORCID,Leick Edna Aparecida1ORCID,Oliva Maria Luiza Vilela4,Martins Milton de Arruda1,Ruiz-Schutz Viviane Christina1ORCID,Righetti Renato Fraga1ORCID,Tibério Iolanda de Fátima Lopes Calvo1ORCID

Affiliation:

1. Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, 01246-903 São Paulo, SP, Brazil

2. Universidade Cidade de São Paulo, São Paulo, SP, Brazil

3. Universidade do Estado de Minas Gerais, 04044-020 Passos, MG, Brazil

4. Departamento de Bioquímica, Universidade Federal de São Paulo, 04044-020 São Paulo, SP, Brazil

5. Departamento de Bioquímica, Universidade Federal de Pernambuco, 50670-910 Recife, PE, Brazil

6. Departamento de Ciências Biológicas, Universidade Federal de São Paulo, 11015-020 Santos, SP, Brazil

Abstract

Background. CrataBL is a protein isolated from Crataeva tapia bark. It has been shown to exhibit several biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. There are no studies evaluating the role of CrataBL in experimental asthma models. Aim. To evaluate the effects of CrataBL on lung mechanics, inflammation, remodeling, and oxidative stress activation of mice with allergic pulmonary inflammation. Materials and Methods. BALB/c mice (6-7 weeks old, 25-30g) were divided into four groups: nonsensitized and nontreated mice (C group, n=8); ovalbumin- (OVA-) sensitized and nontreated mice (OVA group, n=8); nonsensitized and CrataBL-treated mice (C+CR group, n=8); OVA-sensitized and CrataBL-treated mice (OVA+CR group, n=8). We evaluated hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), pulmonary inflammation, extracellular matrix remodeling, and oxidative stress markers. Results. CrataBL treatment in OVA-sensitized mice (OVA+CR group) attenuated the following variables compared to OVA-sensitized mice without treatment (OVA group) (all p<0.05): (1) respiratory system resistance (Rrs) and elastance (Ers) after methacholine challenge; (2) total cells, macrophages, polymorphonuclear cells, and lymphocytes in BALF; (3) eosinophils and volume fraction of collagen and elastic fibers in the airway and alveolar wall according to histopathological and morphometry analysis; (4) IL-4-, IL-5-, IL-13-, IL-17-, IFN-γ-, MMP-9-, TIMP-1-, TGF-β-, iNOS-, and NF-kB-positive cells and volume of 8-iso-PGF2α in airway and alveolar septa according to immunohistochemistry; and (5) IL-4, IL-5, and IFN-γ according to an ELISA. Conclusion. CrataBL contributes to the control of hyperresponsiveness, pulmonary inflammation, extracellular matrix remodeling, and oxidative stress responses in an animal model of chronic allergic pulmonary inflammation.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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