Journal
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
Volume 10, Issue 1, Pages 67-76Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ACI.0b013e328334643a
Keywords
airway; epidermal growth factor; goblet cell; IL-13; mucin
Categories
Ask authors/readers for more resources
Purpose of review Airway mucus hypersecretion is a pathophysiological feature of asthma and, in many patients, contributes to morbidity and mortality. Although current pharmacotherapy is effective in patients with stable disease, severe asthma is poorly treated, and there is no specific treatment for the hypersecretion. Consequently, identification of potential targets for pharmacotherapy of hypersecretion in asthma is warranted. This review identifies intracellular signalling pathways as rational targets for treatment of excessive airway mucus production. Recent findings The inflammatory mediators and the associated intracellular signalling pathways underlying development of goblet cell hyperplasia, an index of mucus hypersecretion, are becoming ever clearer, and include T-helper type 2 (Th2) cytokines, in particular interleukin (IL)-9 and IL-13, as well as IL-1 beta, tumour necrosis factor (TNF)-alpha and cyclooxygenase (COX)-2. IL-9 may act predominantly via calcium-activated chloride channels (CLCAs), IL-13 via STAT-6 and FOXA2, TNF-alpha via nuclear factor (NF)-kappa B, and IL-1 beta via COX-2. Epidermal growth factor receptor (EGF-R) and FOXA2 appear to be convergent pathways for a number of mediator signals, with EGF-R up-regulated in the airways of asthmatic patients. Summary Although many potential intracellular signalling pathways have been identified as possible targets for pharmacotherapy of airway mucus hypersecretion in asthma, the EGFR and Th2 cytokine pathways offer the greatest potential for inhibition of excessive mucus production.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available