%0 Journal Article %A Michael Roth %A Jun Zhong %A Pieter Borger %A Chong Teck S'ng %A Michael Tamm %T Formoterol reduces asthmatic airway smooth muscle cell proliferation through p27 (Kip) which is supported by steroids %D 2012 %J European Respiratory Journal %P P4834 %V 40 %N Suppl 56 %X Background: Airway remodelling in asthma is partly due to increased airway smooth muscle (ASM) mass. We and others reported earlier that steroids alone do not significantly reduce proliferation of ASM cells isolated from asthma patients.Objective: Here, we investigated the anti-proliferative signalling pathway of formoterol combined with three different steroids on ASM cell proliferation control.Methods: Proliferation was determined by cell count 3 days after stimulation. Drugs were used at concentrations 1nM – 1microM. Protein expression (p21, p27) was determined by immuno-blot and -staining. Cyclic AMP was inhibited by DDA pre-incubation.Results: Serum induced proliferation was reduced by steroids (dexamethasone, fluticasone, budesonide) in ASM cells of healthy controls but not of asthma patients. Formoterol dose dependently reduced cell proliferation by maximal 25% in both asthma and control ASM cells and this was paralleled by p27(Kip) activation in asthma ASM cells only. In combination the inhibitory effect of formoterol increased to 52% by dexamethasone, to 69% by budesonide and to 76% by fluticasone in healthy cells. In asthmatic ASM cells the combinded rug's effect was 47%, 52%, an 56% respectively. Inhibition of proliferation of asthmatic ASM cells by formoterol occurred through cAMP and p27(Kip), which were both increased by the addition of steroids. The anti-proliferative effect of the combined drugs in control ASM cells involves p21(Waf1) and in asthmatic cells by p27(Kip).Conclusion: Formoterol activates a disease specific cAMP dependent anti-proliferative signalling in asthmatic ASM cells which is supported by the addition of steroids. %U https://erj.ersjournals.com/content/erj/40/Suppl_56/P4834.full.pdf