p38 MAPK Activation as the Basis for Corticosteroid Insensitivity in Severe Asthma

Detailed Summary

This research aims to find out how the inflammation in patients suffering from severe asthma is different from that in non-severe asthma, and how it may prevent corticosteroids from working efficiently in severe asthma. It will look,in particular, at a protein enzyme called p38 mitogen-activated protein kinase (p38 MAPK for short)which controls the activation of several important pathways in the cell. We wish to find out whether this enzyme is more active in cells obtained from patients with severe asthma compared to those with non-severe asthma. We would like to understand how this enzyme can cause the cell to respond less well to the anti-inflammatory effects of corticosteroids. We also wish to find out whether any specific inhibitors of p38 MAPK can improve severe asthma by improving the effects of corticosteroids on these cells. We hypothesise that activation of the intracellular MAPK signalling pathway underlies the inflammatory processes of severe asthma, and leads to the diminution of the anti-inflammatory actions of CS through histone modification.

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