Imperial College London
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Dr Lynne Sykes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2186l.sykes Website

 
 
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Location

 

3007Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sykes:2015:10.1111/imm.12534,
author = {Sykes, L and Thomson, KR and Boyce, EJ and Lee, YS and Rasheed, ZB and MacIntyre, DA and Teoh, TG and Bennett, PR},
doi = {10.1111/imm.12534},
journal = {Immunology},
pages = {630--644},
title = {Sulfasalazine augments a pro-inflammatory response in IL-1β-stimulated amniocytes and myocytes.},
url = {http://dx.doi.org/10.1111/imm.12534},
volume = {146},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Preterm birth occurs in 10% of pregnancies and is a major cause of neonatal morbidity and mortality. The majority of cases of early preterm labour (PTL) are associated with infection/inflammation, which places the fetal central nervous system at risk. Targeting immune activation is therefore an appealing therapeutic strategy for the prevention of PTL and neonatal brain injury. The expression of many labour-associated and inflammatory-response genes are controlled by the transcription factors NF-κB and Activator Protein-1 (AP-1), which makes them therapeutic targets of interest. Sulfasalazine (SASP) has been shown to inhibit NF-κB and reduce LPS-induced cytokine concentrations in fetal membrane explants and reduce the rate of E.coli-induced PTL in mice. Its effects upon AP-1 in the context of pregnancy are unknown. In this study the effect of SASP on IL-1β-induced NF-κB and AP-1 activity, cytokine production and COX-2 expression was examined in amniocytes and myocytes. A supra-therapeutic concentration (5 mM) was required to inhibit IL-1β-induced NF-κB (p<0.0001) in amniocytes and IL-1β-induced NF-κB (p<0.01), AP-1 (p<0.01) and COX-2 (p<0.05) in myocytes. Despite inhibiting IL-1β-induced cytokines, a basal increase in IL-6 (p<0.01), IL-8 (p<0.0001) and TNF-α (p<0.001) was seen with SASP 5 mM in amniocytes, and significant cytotoxic effects were seen in myocytes. The therapeutic concentration of 0.015 mM had no inhibitory effects on pro-inflammatory mediators, but led to an augmented response to IL-1β-induced IL-6 (p<0.01), IL-8 (p<0.05) and TNF-α (p<0.05) in amniocytes and IL-8 (p<0.05) in myocytes. SASP is therefore an unlikely therapeutic candidate for the prevention of inflammation-induced preterm labour. This article is protected by copyright. All rights reserved.
AU  - Sykes,L
AU  - Thomson,KR
AU  - Boyce,EJ
AU  - Lee,YS
AU  - Rasheed,ZB
AU  - MacIntyre,DA
AU  - Teoh,TG
AU  - Bennett,PR
DO  - 10.1111/imm.12534
EP  - 644
PY  - 2015///
SN  - 0019-2805
SP  - 630
TI  - Sulfasalazine augments a pro-inflammatory response in IL-1β-stimulated amniocytes and myocytes.
T2  - Immunology
UR  - http://dx.doi.org/10.1111/imm.12534
UR  - http://hdl.handle.net/10044/1/27092
VL  - 146
ER  -
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