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PloS one
2015;10 (2): e0118286.

Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

Jianwu Bai, Steven L Smock, George R Jackson, Kenzie D MacIsaac, Yongsheng Huang, Courtney Mankus, Jonathan Oldach, Brian Roberts, Yu-Lu Ma, Joel A Klappenbach, Michael A Crackower, Stephen E Alves, Patrick J Hayden
Author Information
  1. Jianwu Bai: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  2. Steven L Smock: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  3. George R Jackson: MatTek Corporation, Ashland, Massachusetts, United States of America.
  4. Kenzie D MacIsaac: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  5. Yongsheng Huang: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  6. Courtney Mankus: MatTek Corporation, Ashland, Massachusetts, United States of America.
  7. Jonathan Oldach: MatTek Corporation, Ashland, Massachusetts, United States of America.
  8. Brian Roberts: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  9. Yu-Lu Ma: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  10. Joel A Klappenbach: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  11. Michael A Crackower: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  12. Stephen E Alves: Merck Research Laboratories, Boston, Massachusetts, United States of America.
  13. Patrick J Hayden: MatTek Corporation, Ashland, Massachusetts, United States of America.
PMID: 25706956 DOI: 10.1371/journal.pone.0118286

Abstract

OBJECTIVES: Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model.
METHODS: Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively.
MAIN RESULTS: ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1).
CONCLUSIONS: ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

References

  1. Am J Respir Crit Care Med. 2009 Sep 1;180(5):388-95 [PMID: 19483109]
  2. Am J Clin Pathol. 1972 Jun;57(6):737-50 [PMID: 4554720]
  3. Immunol Rev. 2011 Jul;242(1):205-19 [PMID: 21682747]
  4. Virology. 2013 Feb 5;436(1):143-9 [PMID: 23199420]
  5. J Allergy Clin Immunol. 2014 Aug;134(2):332-41 [PMID: 24636084]
  6. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 [PMID: 16199517]
  7. Mucosal Immunol. 2010 Jan;3(1):69-80 [PMID: 19710636]
  8. Am J Respir Crit Care Med. 2014 Mar 1;189(5):532-9 [PMID: 24471509]
  9. Scientifica (Cairo). 2013;2013:405876 [PMID: 24278777]
  10. Am J Respir Cell Mol Biol. 2011 Jun;44(6):739-42 [PMID: 21653905]
  11. Am J Respir Cell Mol Biol. 2006 Feb;34(2):192-203 [PMID: 16210696]
  12. J Investig Med. 2010 Jun;58(5):725-9 [PMID: 20305574]
  13. Am J Respir Cell Mol Biol. 2011 Nov;45(5):1090-100 [PMID: 21642587]
  14. Allergy Asthma Immunol Res. 2013 Nov;5(6):343-7 [PMID: 24179679]
  15. Thorax. 2014 Mar;69(3):240-6 [PMID: 24127021]
  16. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15858-63 [PMID: 17898169]
  17. Am J Respir Cell Mol Biol. 2008 May;38(5):517-23 [PMID: 18063839]
  18. Clin Exp Immunol. 2012 Dec;170(3):365-74 [PMID: 23121677]
  19. In Vitro Cell Dev Biol. 1988 May;24(5):420-8 [PMID: 3372447]
  20. Am J Respir Crit Care Med. 2000 Nov;162(5):1812-8 [PMID: 11069818]
  21. Am J Respir Cell Mol Biol. 2014 Aug;51(2):229-41 [PMID: 24588727]
  22. Chest. 2010 Apr;137(4):812-22 [PMID: 19837822]
  23. Nat Genet. 1997 Apr;15(4):389-92 [PMID: 9090385]
  24. J Virol. 2010 Aug;84(15):7418-26 [PMID: 20375160]
  25. J Allergy Clin Immunol. 2009 Jun;123(6):1384-90.e2 [PMID: 19428098]
  26. Am J Physiol Lung Cell Mol Physiol. 2011 Jan;300(1):L25-31 [PMID: 20971803]
  27. J Immunol. 2006 Feb 1;176(3):1860-8 [PMID: 16424217]
  28. J Exp Med. 2005 Mar 21;201(6):937-47 [PMID: 15781584]
  29. Virol J. 2010;7:264 [PMID: 20937137]
  30. Am J Respir Crit Care Med. 2008 Nov 1;178(9):962-8 [PMID: 18658112]
  31. Immunol Rev. 2011 Jul;242(1):69-90 [PMID: 21682739]
  32. J Biol Chem. 2012 Aug 10;287(33):27948-58 [PMID: 22700966]
  33. Am J Respir Cell Mol Biol. 2007 Aug;37(2):169-85 [PMID: 17413031]
  34. Am J Physiol. 1992 Jun;262(6 Pt 1):L713-24 [PMID: 1616056]
  35. Nat Genet. 2014 Jan;46(1):51-5 [PMID: 24241537]
  36. Nat Med. 2006 Sep;12(9):1023-6 [PMID: 16906156]
  37. Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L373-81 [PMID: 14711802]
  38. Virology. 2013 Nov;446(1-2):1-8 [PMID: 24074561]
  39. PLoS One. 2014;9(9):e106501 [PMID: 25203745]
  40. J Allergy Clin Immunol. 2005 Jun;115(6):1148-54 [PMID: 15940127]
  41. Respirology. 2009 Mar;14(2):180-6 [PMID: 19207121]
  42. Clin Exp Allergy. 2014 Jan;44(1):91-101 [PMID: 24131248]
  43. J Allergy Clin Immunol. 2010 Oct;126(4):722-729.e2 [PMID: 20673980]
  44. Nat Genet. 2000 May;25(1):25-9 [PMID: 10802651]

Grants

  1. R43 HL088807/NHLBI NIH HHS
  2. 1R43HL088807-01/NHLBI NIH HHS

MeSH Term

Adolescent
Adult
Asthma
Cell Differentiation
Cells, Cultured
Chemokines
Child
Epithelial Cells
Female
Gene Expression
Humans
Inflammation
Male
Middle Aged
Picornaviridae Infections
Respiratory System
Rhinovirus
Signal Transduction

Chemicals

Chemokines
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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