The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure
Juliana D. Lourenço1, Juliana T. Ito1, Daniela A.B. Cervilha1, Davi S. Sales1, Alyne Riani1, Camila L. Suehiro2, Isabella S. Genaro1,3, Adriana Duran4, Luciano Puzer4, Milton A. Martins1, Sérgio D. Sasaki4 and Fernanda D.T.Q.S. Lopes1
1Department of Medicine, 2Department of Pathology, University of Sao Paulo, 3Hospital Public Employee of Sao Paulo (IAMSPE), Sao Paulo and 4Centro de Ciências Naturais e Humanas, UFABC, Santo Andre, Brazil
Offprint requests to: Fernanda Degobbi Tenorio Quirino dos Santos Lopes, Departamento de Medicina, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 - Sala 1210, São Paulo - SP, CEP 01246-903, Brazil. e-mail: fernandadtqsl@gmail.com or fernanda@experimental.fm.usp.br
Summary. Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase-induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS-induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP-12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels. Histol Histopathol 33, 289-298 (2018)
Key words: Protease inhibitor, Cigarette smoke, Emphysema, Metalloproteases, Animal models
DOI: 10.14670/HH-11-927