PT  - JOURNAL ARTICLE
AU  - Varsha Kanabar
AU  - Rachel Brown
AU  - Domenico Spina
AU  - Clive Page
TI  - The effect of adenosine on VEGF release from airway smooth muscle from subjects with asthma
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P557
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P557.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P557.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - IntroductionAirway smooth muscle cells (ASM) from subjects with mild asthma secrete increased levels of VEGF and increased expression of adenosine A1 receptor in bronchial biopsies compared to healthy subjects. We hypothesised that VEGF release from ASM in asthma is mediated via adenosine A1 receptors.ObjectivesTo examine the effect of adenosine on VEGF release in ASM derived from asthmatic subjects.MethodsASM from healthy (n=4) and mild asthmatic (n=3) subjects were treated with and without adenosine receptor agonists (0.01-100µM) targeting A1 (CPA), A2 (CV1808), A2a (CGS21680), A3 (IB-MECA) or non-selective (adenosine, NECA). ASM were also treated with 10µM NECA following pre-treatment with adenosine receptor antagonists (1-100nM). After 24hr, VEGF levels in cell-conditioned media were determined by ELISA.ResultsConstitutive levels of VEGF in ASM derived from asthmatics (275±34pg/ml/106 cells) were 1.7 fold greater than ASM derived from healthy subjects (159±34pg/ml/106 cells, p<0.05). Activation of each adenosine receptor subtype did not significantly alter basal VEGF release from ASM derived from healthy subjects. However, NECA and CGS21680 concentration dependently increased VEGF release by 1.8- and 2-fold respectively in ASM derived from mild asthmatics compared to unstimulated controls (p<0.05). Pre-treatment of ASM with adenosine receptor antagonists (1-100nM) followed by 10µM NECA revealed that the A2a and A2b receptor antagonist ZM241385 and PSB0788 respectively, both significantly inhibited NECA-induced VEGF release (P<0.05).ConclusionsVEGF release induced by adenosine receptor activation in ASM derived from mild asthmatic subjects was mediated through A2a and A2b receptors.