Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles

Carregando...
Imagem de Miniatura
Citações na Scopus
14
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citação
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v.167, p.494-504, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Endogenous acetylcholine (ACh), which depends of the levels of vesicular ACh transport (VAChT) to be released, is the central mediator of the cholinergic anti-inflammatory system. ACh controls the release of cytokine in different models of inflammation. Diesel exhaust particles (DEP) are one of the major environmental pollutants produced in large quantity by automotive engines in urban center. DEP bind the lung parenchyma and induce inflammation. We evaluated whether cholinergic dysfunction worsens DEP-induced lung inflammation. Male mice with decreased ACh release due to reduced expression of VAChT (VAChT-KD mice) were submitted to DEP exposure for 30 days (3 mg/mL of DEP, once a day, five days a week) or saline. Pulmonary function and inflammation as well as extracellular matrix fiber deposition were evaluated. Additionally, airway and nasal epithelial mucus production were quantified. We found that DEP instillation worsened lung function and increased lung inflammation. Higher levels of mononuclear cells were observed in the peripheral blood of both wild-type (WT) and VAChT-KD mice. Also, both wild-type (WT) and VAChT-KD mice showed an increase in macrophages in bronchoalveolar lavage fluid (BALF) as well as increased expression of IL-4, IL-6, IL-13, TNF-alpha, and NF-kappa B in lung cells. The collagen fiber content in alveolar septa was also increased in both genotypes. On the other hand, we observed that granulocytes were increased only in VAChT-KD peripheral blood. Likewise, increased BALF lymphocytes and neutrophils as well as increased elastic fibers in alveolar septa, airway neutral mucus, and nasal epithelia acid mucus were observed only in VAChT-KD mice. The cytokines IL-4 and TNF-alpha were also higher in VAChT-KD mice compared with WT mice. In conclusion, decreased ability to release ACh exacerbates some of the lung alterations induced by DEP in mice, suggesting that VAChT-KD animals are more vulnerable to the effects of DEP in the lung.
Palavras-chave
Air pollution, Acetylcholine, Pulmonary inflammation, Cholinergic anti-inflammatory system, VAChT
Referências
  1. Araujo BB, 2008, EUR RESPIR J, V32, P61, DOI 10.1183/09031936.00147807
  2. Bai N, 2013, INHAL TOXICOL, V25, P725, DOI 10.3109/08958378.2013.844749
  3. Barton DB, 2014, CELL TISSUE RES, V358, P229, DOI 10.1007/s00441-014-1905-x
  4. Behndig AF, 2006, EUR RESPIR J, V27, P359, DOI 10.1183/09031936.06.00136904
  5. Belmonte Kristen E, 2005, Proc Am Thorac Soc, V2, P297, DOI 10.1513/pats.200504-043SR
  6. Bernik TR, 2002, J EXP MED, V195, P781, DOI 10.1084/jem.20011714
  7. BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  8. Brook RD, 2010, CIRCULATION, V121, P2331, DOI 10.1161/CIR.0b013e3181dbece1
  9. Brunekreef B, 2002, LANCET, V360, P1233, DOI 10.1016/S0140-6736(02)11274-8
  10. Chen ZY, 2017, EXP THER MED, V14, P3485, DOI 10.3892/etm.2017.4937
  11. Daviskas E, 2006, J AEROSOL MED, V19, P100, DOI 10.1089/jam.2006.19.100
  12. de Castro BM, 2009, MOL CELL BIOL, V29, P5238, DOI 10.1128/MCB.00245-09
  13. DOCKERY DW, 1993, NEW ENGL J MED, V329, P1753, DOI 10.1056/NEJM199312093292401
  14. Gavett SH, 2003, ENVIRON HEALTH PERSP, V111, P1471, DOI 10.1289/ehp.6300
  15. Ghio AJ, 2001, AM J RESP CRIT CARE, V164, P704, DOI 10.1164/ajrccm.164.4.2011089
  16. Gosens R, 2018, EUR RESPIR J, V52, DOI 10.1183/13993003.01247-2017
  17. Gundavarapu S, 2012, J ALLERGY CLIN IMMUN, V130, P770, DOI 10.1016/j.jaci.2012.04.002
  18. Gwilt CR, 2007, PHARMACOL THERAPEUT, V115, P208, DOI 10.1016/j.pharmthera.2007.05.007
  19. HANTOS Z, 1992, J APPL PHYSIOL, V72, P168
  20. Hiura TS, 1999, J IMMUNOL, V163, P5582
  21. Inoue K, 2009, EXP BIOL MED, V234, P200, DOI 10.3181/0809-RM-285
  22. Ishihara Y, 2002, INHAL TOXICOL, V14, P1049, DOI 10.1080/08958370290084773
  23. James AL, 2012, AM J RESP CRIT CARE, V185, P1058, DOI 10.1164/rccm.201110-1849OC
  24. Jeremias IC, 2016, MOL NEUROBIOL, V53, P6635, DOI 10.1007/s12035-015-9538-y
  25. Kampa M, 2008, ENVIRON POLLUT, V151, P362, DOI 10.1016/j.envpol.2007.06.012
  26. Kodavanti UP, 2013, TOXICOL APPL PHARM, V268, P232, DOI 10.1016/j.taap.2013.02.002
  27. Lara A, 2010, MOL CELL BIOL, V30, P1746, DOI 10.1128/MCB.00996-09
  28. Lehmann AD, 2009, PART FIBRE TOXICOL, V6, DOI 10.1186/1743-8977-6-26
  29. Leite HR, 2016, BRAIN BEHAV IMMUN, V57, P282, DOI 10.1016/j.bbi.2016.05.005
  30. Li DJ, 2011, HYPERTENSION, V57, P298, DOI 10.1161/HYPERTENSIONAHA.110.160077
  31. Li N, 2002, J IMMUNOL, V169, P4531, DOI 10.4049/jimmunol.169.8.4531
  32. Li P, 2016, EXP GERONTOL, V74, P43, DOI 10.1016/j.exger.2015.12.005
  33. Li RJ, 2007, REGUL TOXICOL PHARM, V48, P284, DOI 10.1016/j.yrtph.2007.04.009
  34. Lips KS, 2007, LIFE SCI, V80, P2263, DOI 10.1016/j.lfs.2007.01.026
  35. Massa CB, 2017, PLOS COMPUT BIOL, V13, DOI 10.1371/journal.pcbi.1005570
  36. Mauad T, 2007, J ALLERGY CLIN IMMUN, V120, P997, DOI 10.1016/j.jaci.2007.06.031
  37. Nemmar A, 2012, TOXICOLOGY, V292, P162, DOI 10.1016/j.tox.2011.12.009
  38. Parrish WR, 2008, MOL MED, V14, P567, DOI 10.2119/2008-00079.Parrish
  39. Pinheiro NM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0120441
  40. Pires-Neto RC, 2006, ENVIRON RES, V101, P356, DOI 10.1016/j.envres.2005.12.018
  41. Prado MAM, 2002, NEUROCHEM INT, V41, P291, DOI 10.1016/S0197-0186(02)00044-X
  42. Prado VF, 2013, BIOCHEM J, V450, P265, DOI 10.1042/BJ20121662
  43. Prado VF, 2006, NEURON, V51, P601, DOI 10.1016/j.neuron.2006.08.005
  44. Proskocil BJ, 2004, ENDOCRINOLOGY, V145, P2498, DOI 10.1210/en.2003-1728
  45. RighettI RF, 2014, RESP PHYSIOL NEUROBI, V192, P134, DOI 10.1016/j.resp.2013.12.012
  46. Rosas-Ballina M, 2009, J INTERN MED, V265, P663, DOI 10.1111/j.1365-2796.2009.02098.x
  47. Rosas-Ballina M, 2011, SCIENCE, V334, P98, DOI 10.1126/science.1209985
  48. Roy A, 2014, MOL MED, V20, P527, DOI 10.2119/molmed.2014.00125
  49. Roy A, 2013, FASEB J, V27, P5072, DOI 10.1096/fj.13-238279
  50. Sagai M, 1996, FREE RADICAL BIO MED, V21, P199, DOI 10.1016/0891-5849(96)00032-9
  51. Salvi S, 1999, AM J RESP CRIT CARE, V159, P702, DOI 10.1164/ajrccm.159.3.9709083
  52. Sango K, 1996, NAT GENET, V14, P348, DOI 10.1038/ng1196-348
  53. Schuliga M, 2015, BIOMOLECULES, V5, P1266, DOI 10.3390/biom5031266
  54. SCHWARTZ J, 1994, AM J RESP CRIT CARE, V150, P1234, DOI 10.1164/ajrccm.150.5.7952546
  55. Seriani R, 2015, ENVIRON TOXICOL, V30, P1297, DOI 10.1002/tox.22000
  56. Smith R, 2006, HUM MOL GENET, V15, P3119, DOI 10.1093/hmg/ddl252
  57. Stenfors N, 2004, EUR RESPIR J, V23, P82, DOI 10.1183/09031936.03.00004603
  58. Tanaka M, 2013, J TOXICOL SCI, V38, P35, DOI 10.2131/jts.38.35
  59. Terry AV, 2007, NEUROSCIENCE, V146, P1316, DOI 10.1016/j.neuroscience.2007.03.003
  60. Toledo AC, 2013, BRIT J PHARMACOL, V168, P1736, DOI 10.1111/bph.12062
  61. Win-Shwe TT, 2013, J TOXICOL SCI, V38, P71, DOI 10.2131/jts.38.71
  62. Yanamala N, 2013, TOXICOL APPL PHARM, V272, P373, DOI 10.1016/j.taap.2013.07.006
  63. Yang X, 2014, QJM-INT J MED, V107, P789, DOI 10.1093/qjmed/hcu005
  64. Yoshizaki K, 2010, INHAL TOXICOL, V22, P610, DOI 10.3109/08958371003621633
  65. Yoshizaki K, 2015, RESP RES, V16, DOI [10.1186/s12931-15-0172-z, 10.1186/s12931-015-0172-z]