Imperial College London
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DrMarkBirrell

Faculty of Medicine, National Heart & Lung Institute

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 8578m.birrell

 
 
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Location

 

103Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kaur:2015:10.1016/j.pupt.2015.09.002,
author = {Kaur, M and Birrell, MA and Dekkak, B and Reynolds, S and Wong, S and De, Alba J and Raemdonck, K and Hall, S and Simpson, K and Begg, M and Belvisi, MG and Singh, D},
doi = {10.1016/j.pupt.2015.09.002},
journal = {Pulmonary Pharmacology & Therapeutics},
pages = {67--74},
title = {The role of CRAC channel in asthma},
url = {http://dx.doi.org/10.1016/j.pupt.2015.09.002},
volume = {35},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Asthma is increasing globally and current treatments only manage a proportion of patients. There is an urgent need to develop new therapies. Lymphocytes are thought to play a central role in the pathophysiology of asthma through the production of inflammatory mediators. This is thought to be via the transcription factor NFAT which in turn can be activated through Ca2+ release-activated Ca2+ (CRAC) channels. The aim of this work was to investigate the role of CRAC in clinical and pre-clinical models of allergic asthma.Initial data demonstrated that the NFAT pathway is increased in stimulated lymphocytes from asthmatics. To confirm a role for the channel we showed that a selective inhibitor, Synta 66, blocked mediator production from lymphocytes. Synta 66 inhibited CD2/3/28 induced IL-2, IL-7, IL-13 & IFNΥ in a concentration-dependent manner in healthy and severe asthma donors, with over 60% inhibition observed for all cytokines. NFAT pathway was also increased in a pre-clinical asthma model. In this model we have demonstrated that CRAC played a central role in the airway inflammation and late asthmatic response (LAR). In conclusion, our data provides evidence that suggests targeting CRAC channels could be of therapeutic benefit for asthma sufferers.
AU  - Kaur,M
AU  - Birrell,MA
AU  - Dekkak,B
AU  - Reynolds,S
AU  - Wong,S
AU  - De,Alba J
AU  - Raemdonck,K
AU  - Hall,S
AU  - Simpson,K
AU  - Begg,M
AU  - Belvisi,MG
AU  - Singh,D
DO  - 10.1016/j.pupt.2015.09.002
EP  - 74
PY  - 2015///
SN  - 1522-9629
SP  - 67
TI  - The role of CRAC channel in asthma
T2  - Pulmonary Pharmacology & Therapeutics
UR  - http://dx.doi.org/10.1016/j.pupt.2015.09.002
UR  - http://hdl.handle.net/10044/1/32276
VL  - 35
ER  -
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