The Effect of Long Acting Muscarinic Antagonists on Corticosteroid Action in Airway Smooth Muscle Cells in Asthma (360G-Wellcome-206781_Z_17_Z)
Severe asthmatics are less responsive to the positive therapeutic effects of corticosteroid therapy. Identifying therapies to overcome this steroid resistance is a key goal of research. Current research has shown that molecular interactions between glucocorticoid receptors (GR) and G protein-coupled beta receptors exist. However, less is known regarding the interaction between GR and muscarinic receptors (M2, M3) and on the effect of long-acting muscarinic antagonists (LAMAs) on corticosteroid insensitivity in severe asthmatics. This proposal aims to ascertain whether corticosteroids used in conjunction with muscarinic antagonists will enhance the suppressive effect of steroids on inflammatory mediator release from airway smooth muscle cells (ASMC) in severe asthmatics. By measuring inflammatory mediators using ELISA, and investigating gene expression via real-time qPCR of isolated RNA from ASMC of severe asthmatics; the effects of i) muscarinic antagonists alone, ii) corticosteroids alone and iii) muscarinic antagonists given in conjunction with corticosteroids, can be compared. The results will then be statistically analysed to compare and identify any significant differences in inflammatory mediator release when using muscarinic antagonists and corticosteroids together, and when using them separately. The objective of this project is to advance current knowledge of the therapeutic benefits of these treatments for asthma.
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