The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure
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11
Tipo de produção
article
Data de publicação
2018
Editora
F HERNANDEZ
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Título do Volume
Autores
GENARO, Isabella S.
DURAN, Adriana
PUZER, Luciano
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Citação
HISTOLOGY AND HISTOPATHOLOGY, v.33, n.3, p.289-298, 2018
Resumo
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.
Palavras-chave
Protease inhibitor, Cigarette smoke, Emphysema, Metalloproteases, Animal models
Referências
- Belvisi MG, 2003, INFLAMM RES, V52, P95, DOI 10.1007/s000110300020
- Biselli PJC, 2011, BRAZ J MED BIOL RES, V44, P460, DOI 10.1590/S0100-879X2011007500040
- Churg A, 2004, AM J RESP CRIT CARE, V170, P492, DOI 10.1164/rccm.200404-5110C
- Churg A, 2012, EUR RESPIR J, V39, P197, DOI 10.1183/09031936.00121611
- Churg A, 2007, THORAX, V62, P706, DOI 10.1136/thx.2006.068353
- Churg A, 2009, AM J RESP CELL MOL, V40, P482, DOI 10.1165/rcmb.2008-0038OC
- Dhami R, 2000, AM J RESP CELL MOL, V22, P244, DOI 10.1165/ajrcmb.22.2.3809
- Dolhnikoff M, 1999, AM J RESP CRIT CARE, V160, P1750, DOI 10.1164/ajrccm.160.5.9812040
- Finlay GA, 1997, AM J RESP CRIT CARE, V156, P240, DOI 10.1164/ajrccm.156.1.9612018
- Fricker M, 2014, EXPERT OPIN DRUG DIS, V9, P629, DOI 10.1517/17460441.2014.909805
- Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2015, EX SUMM GLOB STRAT D
- Gueders MM, 2006, EUR J PHARMACOL, V533, P133, DOI 10.1016/j.ejphar.2005.12.082
- HANTOS Z, 1992, J APPL PHYSIOL, V72, P168
- Hautamaki RD, 1997, SCIENCE, V277, P2002, DOI 10.1126/science.277.5334.2002
- Kassim S. Y., 2005, J BIOL CHEM
- Kuraki T, 2002, AM J RESP CRIT CARE, V166, P496, DOI 10.1164/rccm.2103118
- Lim S, 2000, AM J RESP CRIT CARE, V162, P1355, DOI 10.1164/ajrccm.162.4.9910097
- Lopes FDTQS, 2013, HISTOL HISTOPATHOL, V28, P269, DOI 10.14670/HH-28.269
- Lourenco JD, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0098216
- Mahadeva R, 2002, THORAX, V57, P908, DOI 10.1136/thorax.57.10.908
- Ofulue AF, 1998, AM J PHYSIOL-LUNG C, V275, pL1134
- Robertoni FSZ, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0129590
- Russell REK, 2002, AM J RESP CELL MOL, V26, P602, DOI 10.1165/ajrcmb.26.5.4685
- Shapiro SD, 1998, CURR OPIN CELL BIOL, V10, P602, DOI 10.1016/S0955-0674(98)80035-5
- Shapiro SD, 2003, AM J PATHOL, V163, P2329, DOI 10.1016/S0002-9440(10)63589-4
- Shipley JM, 1996, P NATL ACAD SCI USA, V93, P3942, DOI 10.1073/pnas.93.9.3942
- Soares TS, 2016, VET PARASITOL, V219, P44, DOI 10.1016/j.vetpar.2016.01.021
- Toledo AC, 2012, EUR RESPIR J, V39, P254, DOI 10.1183/09031936.00003411
- WEIBEL ER, 1966, J CELL BIOL, V30, P23, DOI 10.1083/jcb.30.1.23
- Willadsen P, 1999, PARASITOL TODAY, V15, P258, DOI 10.1016/S0169-4758(99)01472-6
- Wright JL, 2002, AM J RESP CRIT CARE, V166, P954, DOI 10.1164/rccm.200202-098OC
- WRIGHT JL, 1990, AM REV RESPIR DIS, V142, P1422, DOI 10.1164/ajrccm/142.6_Pt_1.1422
- Wright JL, 2008, AM J PHYSIOL-LUNG C, V295, pL1, DOI 10.1152/ajplung.90200.2008