Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

Carregando...
Imagem de Miniatura
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2017
Título da Revista
ISSN da Revista
Título do Volume
Editora
HINDAWI LTD
Autores
ALMEIDA-REIS, Rafael
THEODORO-JUNIOR, Osmar A.
OLIVA, Leandro V.
BONTURI, Camila R.
BRITO, Marlon V.
PRADO, Carla M.
Citação
BIOMED RESEARCH INTERNATIONAL, article ID 8287125, 13p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods. C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF alpha-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 alpha, collagen,and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF alpha-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.
Palavras-chave
Referências
  1. Araujo APU, 2005, BIOL CHEM, V386, P561, DOI 10.1515/BC.2005.066
  2. Barnes PJ, 2005, EUR RESPIR J, V25, P1084, DOI 10.1183/09031936.05.00139104
  3. Churg A, 2005, CURR OPIN PULM MED, V11, P153, DOI 10.1097/01.mcp.0000149592.51761.e3
  4. De Leo F, 2002, NUCLEIC ACIDS RES, V30, P347, DOI 10.1093/nar/30.1.347
  5. de Oliveira C, 2001, BIOL CHEM, V382, P847, DOI 10.1515/BC.2001.103
  6. Deshmukh HS, 2005, AM J RESP CRIT CARE, V171, P305, DOI 10.1164/rccm.200408-1003OC
  7. Drag M, 2010, NAT REV DRUG DISCOV, V9, P690, DOI 10.1038/nrd3053
  8. Fromer L, 2008, INT J CLIN PRACT, V62, P1219, DOI 10.1111/j.1742-1241.2008.01807.x
  9. Fujie K, 1999, INFLAMM RES, V48, P160, DOI 10.1007/s000110050440
  10. Guarnieri F, 2010, P NATL ACAD SCI USA, V107, P10661, DOI 10.1073/pnas.1001349107
  11. Hanaoka M, 2011, CHEST, V139, P1101, DOI 10.1378/chest.10-0920
  12. Hantos Z, 2003, J APPL PHYSIOL, V95, P1695, DOI 10.1152/japplphysiol.00104.2003
  13. Hantos Z, 2008, J APPL PHYSIOL, V105, P1864, DOI 10.1152/japplphysiol.90924.2008
  14. Hautamaki RD, 1997, SCIENCE, V277, P2002, DOI 10.1126/science.277.5334.2002
  15. Ito S, 2004, J APPL PHYSIOL, V97, P204, DOI 10.1152/japplphysiol.01246.2003
  16. Kim Suil, 2004, Treat Respir Med, V3, P147, DOI 10.2165/00151829-200403030-00003
  17. Korkmaz B, 2010, PHARMACOL REV, V62, P726, DOI 10.1124/pr.110.002733
  18. LAURELL CB, 1963, SCAND J CLIN LAB INV, V15, P132, DOI 10.3109/00365516309051324
  19. Lopes FDTQS, 2013, HISTOL HISTOPATHOL, V28, P269, DOI 10.14670/HH-28.269
  20. Luisetti M, 1996, EUR RESPIR J, V9, P1482, DOI 10.1183/09031936.96.09071482
  21. Mahadeva R, 2002, THORAX, V57, P908, DOI 10.1136/thorax.57.10.908
  22. Martins-Olivera B. T., 2016, MEDIAT INFLAMM, V2016
  23. Neuhof C, 2003, BIOL CHEM, V384, P939, DOI 10.1515/BC.2003.105
  24. Oliva LV, 2015, PROCESS BIOCHEM, V50, P1958, DOI 10.1016/j.procbio.2015.06.004
  25. Oliva MLV, 2009, AN ACAD BRAS CIENC, V81, P615, DOI 10.1590/S0001-37652009000300023
  26. Oliveira C, 2010, BRIT J PHARMACOL, V161, P899, DOI 10.1111/j.1476-5381.2010.00924.x
  27. Owen CA, 1999, J LEUKOCYTE BIOL, V65, P137
  28. Owen Caroline A, 2008, Int J Chron Obstruct Pulmon Dis, V3, P253
  29. Pauwels Romain A., 2001, American Journal of Respiratory and Critical Care Medicine, V163, P1256
  30. Prado CM, 2005, AM J PHYSIOL-LUNG C, V288, pL741, DOI 10.1152/ajplung.00208.2004
  31. Scuri M, 2000, J APPL PHYSIOL, V89, P1397
  32. Selman M, 2003, CHEST, V123, P1633, DOI 10.1378/chest.123.5.1633
  33. Shapiro S D, 2003, Eur Respir J Suppl, V44, p30s
  34. Shapiro SD, 2003, AM J PATHOL, V163, P2329, DOI 10.1016/S0002-9440(10)63589-4
  35. Suzuki M, 2009, AM J PHYSIOL-LUNG C, V296, pL614, DOI 10.1152/ajplung.90443.2008
  36. Toledo AC, 2011, RESP PHYSIOL NEUROBI, V177, P155, DOI 10.1016/j.resp.2011.03.016
  37. Turk B, 2006, NAT REV DRUG DISCOV, V5, P785, DOI 10.1038/nrd2092
  38. Oliva MLV, 2008, BIOL CHEM, V389, P1007, DOI 10.1515/BC.2008.119
  39. Weibel ER, 2006, J APPL PHYSIOL, V100, P1419, DOI 10.1152/japplphysiol.01301.2005
  40. Wright JL, 2003, EUR RESPIR J, V22, P77, DOI 10.1183/09031936.03.00095703