Imperial College London
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DrBlerinaAhmetaj-Shala

Faculty of Medicine, National Heart & Lung Institute

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7351 8137b.ahmetaj

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kirkby:2016:10.1073/pnas.1517642113,
author = {Kirkby, NS and Chan, MV and Zaiss, AK and Garcia-Vaz, E and Jiao, J and Berglund, LM and Verdu, EF and Ahmetaj-Shala, B and Wallace, JL and Herschman, HR and Gomez, MF and Mitchell, JA},
doi = {10.1073/pnas.1517642113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {434--439},
title = {Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways},
url = {http://dx.doi.org/10.1073/pnas.1517642113},
volume = {113},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system.
AU  - Kirkby,NS
AU  - Chan,MV
AU  - Zaiss,AK
AU  - Garcia-Vaz,E
AU  - Jiao,J
AU  - Berglund,LM
AU  - Verdu,EF
AU  - Ahmetaj-Shala,B
AU  - Wallace,JL
AU  - Herschman,HR
AU  - Gomez,MF
AU  - Mitchell,JA
DO  - 10.1073/pnas.1517642113
EP  - 439
PY  - 2016///
SN  - 1091-6490
SP  - 434
TI  - Systematic study of constitutive cyclo-oxygenase-2 expression: role of NFκB and NFAT transcriptional pathways
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.1517642113
UR  - https://www.pnas.org/content/113/2/434/
UR  - http://hdl.handle.net/10044/1/28551
VL  - 113
ER  -
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