Imperial College London
Dr Benjamin Garfield

DrBenjaminGarfield

Faculty of Medicine, Department of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

b.garfield

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Price:2015:10.1186/s12931-015-0262-y,
author = {Price, LC and Shao, D and Meng, C and Perros, F and Garfield, BE and Zhu, J and Montani, D and Dorfmuller, P and Humbert, M and Adcock, IM and Wort, SJ},
doi = {10.1186/s12931-015-0262-y},
journal = {Respiratory Research},
title = {Dexamethasone induces apoptosis in pulmonary arterial smooth musclecells},
url = {http://dx.doi.org/10.1186/s12931-015-0262-y},
volume = {16},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundDexamethasone suppressed inflammation and haemodynamic changes inan animal model of pulmonary arterial hypertension (PAH). A majortarget for dexamethasone actions is NF­κB, which is activated inpulmonary vascular cells and perivascular inflammatory cells in PAH.Reverse remodelling is an important concept in PAH disease therapy,and further to its anti­proliferative effects, we sought to explore whetherdexamethasone augments pulmonary arterial smooth muscle cell(PASMC) apoptosis.MethodsAnalysis of apoptosis markers (caspase 3, in­situ DNA fragmentation)and NF­κB (p65 and phospho­IKK­α/β) activation was performed onlung tissue from rats with monocrotaline (MCT)­induced pulmonaryhypertension (PH), before and after day 14–28 treatment withdexamethasone (5 mg/kg/day). PASMC were cultured from this rat PHmodel and from normal human lung following lung cancer surgery.Following stimulation with TNF­α (10 ng/ml), the effects ofdexamethasone (10 –10 M) and IKK2 (NF­κB) inhibition12345−8 −6−626/08/2015 e.Proofinghttp://eproofing.springer.com/journals/printpage.php?token=z1f6oNo2TW2­b02e3UtS87S7AQ0qS0Cpd07hxhERYg8 3/38(AS602868, 0–3 μM (0­3×10 M) on IL­6 and CXCL8 release andapoptosis was determined by ELISA and by Hoechst staining. NF­κBactivation was measured by TransAm assay.ResultsDexamethasone treatment of rats with MCT­induced PH in vivo led toPASMC apoptosis as displayed by increased caspase 3 expression andDNA fragmentation. A similar effect was seen in vitro using TNF­α­simulated human and rat PASMC following both dexamethasone andIKK2 inhibition. Increased apoptosis was associated with a reduction inNF­κB activation and in IL­6 and CXCL8 release from PASMC.ConclusionsDexamethasone exerted reverse­remodelling effects by augmentingapoptosis and reversing inflammation in PASMC possibly via i
AU  - Price,LC
AU  - Shao,D
AU  - Meng,C
AU  - Perros,F
AU  - Garfield,BE
AU  - Zhu,J
AU  - Montani,D
AU  - Dorfmuller,P
AU  - Humbert,M
AU  - Adcock,IM
AU  - Wort,SJ
DO  - 10.1186/s12931-015-0262-y
PY  - 2015///
SN  - 1465-993X
TI  - Dexamethasone induces apoptosis in pulmonary arterial smooth musclecells
T2  - Respiratory Research
UR  - http://dx.doi.org/10.1186/s12931-015-0262-y
UR  - http://hdl.handle.net/10044/1/26288
VL  - 16
ER  -
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