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Cigarette smoke and α,β-unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung fibroblasts.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2011 Jun; Vol. 163 (3), pp. 649-61. - Publication Year :
- 2011
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Abstract
- Background and Purpose: Vascular endothelial growth factor (VEGF) is an angiogenic factor known to be elevated in the sputum of asymptomatic smokers as well as smokers with bronchitis type of chronic obstructive pulmonary disease. The aim of this study was to investigate whether acute exposure to cigarette smoke extract altered VEGF production in lung parenchymal cells.<br />Experimental Approach: We exposed human airway smooth muscle cells (ASMC), normal human lung fibroblasts (NHLF) and small airways epithelial cells (SAEC) to aqueous cigarette smoke extract (CSE) in order to investigate the effect of cigarette smoke on VEGF expression and release.<br />Key Results: Vascular endothelial growth factor release was elevated by sub-toxic concentrations of CSE in both ASMC and NHLF, but not in SAEC. CSE-evoked VEGF release was mimicked by its component acrolein at concentrations (10-100 µM) found in CSE, and prevented by the antioxidant and α,β-unsaturated aldehyde scavenger, N-acetylcysteine (NAC). Both CSE and acrolein (30 µM) induced VEGF mRNA expression in ASMC cultures, suggesting an effect at transcriptional level. Crotonaldehyde and 4-hydroxy-2-nonenal, an endogenous α,β-unsaturated aldehyde, stimulated VEGF release, as did H(2)O(2). CSE-evoked VEGF release was accompanied by rapid and lasting phosphorylation of p38 MAPK (mitogen-activated protein kinase), which was abolished by NAC and mimicked by acrolein. Both CSE- and acrolein-evoked VEGF release were blocked by selective inhibition of p38 MAPK signalling.<br />Conclusions and Implications: α,β-Unsaturated aldehydes and possibly reactive oxygen species contained in cigarette smoke stimulate VEGF expression and release from pulmonary cells through p38 MAPK signalling.<br /> (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)
- Subjects :
- Acetylcysteine pharmacology
Bronchi cytology
Bronchi drug effects
Bronchi metabolism
Calcium Channels
Cells, Cultured
Complex Mixtures pharmacology
Fibroblasts metabolism
Humans
Lung cytology
Lung metabolism
Myocytes, Smooth Muscle metabolism
Nerve Tissue Proteins antagonists & inhibitors
Nicotinic Antagonists pharmacology
Phosphorylation
RNA, Messenger metabolism
TRPA1 Cation Channel
Transient Receptor Potential Channels antagonists & inhibitors
Vascular Endothelial Growth Factor A genetics
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases metabolism
Acrolein pharmacology
Aldehydes pharmacology
Fibroblasts drug effects
Lung drug effects
Myocytes, Smooth Muscle drug effects
Smoke adverse effects
Nicotiana
Vascular Endothelial Growth Factor A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 163
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21306579
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2011.01253.x