Document Detail

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells.
MedLine Citation:
PMID:  20817708     Owner:  NLM     Status:  MEDLINE    
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 IPDI-BEAS-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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-03
Journal Detail:
Title:  The European respiratory journal     Volume:  37     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-31     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1226-36     Citation Subset:  IM    
Institute of Clinical Medicine, Kaohsiung Medical University, Taiwan.
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MeSH Terms
Bronchi / drug effects,  secretion
Cell Line
Cell Movement / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Enzyme Inhibitors / pharmacology
Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors,  biosynthesis
Interleukin-8 / biosynthesis*,  secretion*
Isocyanates / pharmacology*
Mitogen-Activated Protein Kinase 1 / biosynthesis
Mitogen-Activated Protein Kinase 3 / biosynthesis
Muscle, Smooth / drug effects*
Proto-Oncogene Proteins c-akt / biosynthesis
RNA, Small Interfering / pharmacology
Signal Transduction / drug effects*
rho GTP-Binding Proteins / antagonists & inhibitors,  biosynthesis
src-Family Kinases / biosynthesis
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Interleukin-8; 0/Isocyanates; 0/RNA, Small Interfering; 43B0856528/isophorone diisocyanate; EC Adhesion Protein-Tyrosine Kinases; EC Kinases; EC Proteins c-akt; EC protein, human; EC Protein Kinase 1; EC Protein Kinase 3; EC protein, human; EC GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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