Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells

P. L. Kuo, M. S. Huang, S. K. Huang, W. C. Ni, J. Y. Hung, Y. C. Ko, C. H. Hung, Y. M. Tsai, T. H. Duh, Y. L. Hsu

Research output: Contribution to journalArticle

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Abstract

This study is the first to analyse the soluble factors secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMCs). We treated immortalised, nontumorigenic human bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the conditioned culture media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs. Exposure of BEAS-2B cells and HBECs to IPDI increased interleukin (IL)-8 production. Culture of BSMCs with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC proliferation and migration, which are major features in asthma-related airway remodelling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK)1/2 and AKT activation. Blocking FAK with a specific inhibitor significantly decreased BSMC migration and proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also decreased IPDIBEAS- 2B-CM-, IPDI-HBEC-CM- and recombinant human IL-8-mediated BSMC proliferation and migration, whereas blocking Rnd3 using small interfering RNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved in the regulation of BSMC migration. Our study suggests that inhibition of IL-8 or IL-8-mediated FAK/ERK/Rnd3 signalling is an attractive therapeutic target for IPDI-mediated asthma. Copyright

Original languageEnglish
Pages (from-to)1226-1236
Number of pages11
JournalEuropean Respiratory Journal
Volume37
Issue number5
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

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Interleukin-8
Smooth Muscle Myocytes
Epithelial Cells
Cell Movement
Focal Adhesion Protein-Tyrosine Kinases
Cell Proliferation
Focal Adhesion Kinase 2
isophorone diisocyanate
Asthma
Airway Remodeling
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Conditioned Culture Medium
Small Interfering RNA
Statistical Factor Analysis
Epithelium
Cell Line

Keywords

  • Interleukin-8
  • Isophorone diisocyanate
  • Migration
  • Occupational asthma
  • Proliferation
  • Rnd3

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells. / Kuo, P. L.; Huang, M. S.; Huang, S. K.; Ni, W. C.; Hung, J. Y.; Ko, Y. C.; Hung, C. H.; Tsai, Y. M.; Duh, T. H.; Hsu, Y. L.

In: European Respiratory Journal, Vol. 37, No. 5, 01.05.2011, p. 1226-1236.

Research output: Contribution to journalArticle

Kuo, PL, Huang, MS, Huang, SK, Ni, WC, Hung, JY, Ko, YC, Hung, CH, Tsai, YM, Duh, TH & Hsu, YL 2011, 'Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells', European Respiratory Journal, vol. 37, no. 5, pp. 1226-1236. https://doi.org/10.1183/09031936.00192109
Kuo, P. L. ; Huang, M. S. ; Huang, S. K. ; Ni, W. C. ; Hung, J. Y. ; Ko, Y. C. ; Hung, C. H. ; Tsai, Y. M. ; Duh, T. H. ; Hsu, Y. L. / Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells. In: European Respiratory Journal. 2011 ; Vol. 37, No. 5. pp. 1226-1236.
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