Imperial College London
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ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
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Location

 

304Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Xu:2019:10.1016/j.ejphar.2018.11.010,
author = {Xu, M and Li, F and Wang, M and Zhang, H and Xu, L and Adcock, IM and Chung, KF and Zhang, Y},
doi = {10.1016/j.ejphar.2018.11.010},
journal = {European Journal of Clinical Pharmacology},
pages = {373--383},
title = {Protective effects of VGX-1027 in PM2.5-induced airway inflammation and bronchial hyperresponsiveness},
url = {http://dx.doi.org/10.1016/j.ejphar.2018.11.010},
volume = {842},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Fine particulate matter (PM2.5) can penetrate into alveolar spaces and induce airway inflammation. Recent evidence suggests that the activation of Toll-like receptor 4 (TLR4) signaling may participate in PM2.5-induced acute lung injury. We investigated the effect of VGX-1027, a TLR4 blocker, on PM2.5-induced airway inflammation and bronchial hyperresponsiveness (BHR) in a murine model in vivo and on inflammatory mechanisms in vitro in human airway epithelial cells. Mice were injected intraperitoneally with vehicle (PBS) or VGX-1027 (25mg/kg) one hour before intranasal instillation of vehicle (PBS) or PM2.5 (7.8mg/kg) for two consecutive days and inflammatory events and BHR studied 24h later. Human airway epithelial Beas-2b cells were pretreated with vehicle or VGX-1027 (50μM) in vitro one hour before incubation with vehicle or PM2.5 (150ng/ml) for 24h and effects on inflammatory mediators and mechanisms studied. VGX-1027 pretreatment attenuated PM2.5-induced BHR and elevated total and neutrophils, macrophages, lymphocytes and eosinophils numbers in bronchoalveolar lavage (BAL) fluid in vivo. PM2.5-induced BAL fluid inflammatory mediator levels including TNF-α, chemokine (C-X-C motif) ligand1, IL-1β, IL-6 and IL-18 were reduced by VGX-1027. PM2.5-induced increases in TNF-α, IL-1β, IL-6 and IL-18 mRNA levels in Beas-2b cells were also reduced by VGX-1027. Mechanistically, VGX-1027 inhibited PM2.5-induced activation of the TLR4-NF-κB-p38 MAPK and NLRP3-caspase-1 pathways as well as the dysregulation of mitochondrial fusion/fission proteins in vivo and in vitro. VGX-1027 may be a potential prophylactic treatment for PM2.5-induced acute lung injury that has airway inflammation, BHR and mitochondrial damage.
AU  - Xu,M
AU  - Li,F
AU  - Wang,M
AU  - Zhang,H
AU  - Xu,L
AU  - Adcock,IM
AU  - Chung,KF
AU  - Zhang,Y
DO  - 10.1016/j.ejphar.2018.11.010
EP  - 383
PY  - 2019///
SN  - 0031-6970
SP  - 373
TI  - Protective effects of VGX-1027 in PM2.5-induced airway inflammation and bronchial hyperresponsiveness
T2  - European Journal of Clinical Pharmacology
UR  - http://dx.doi.org/10.1016/j.ejphar.2018.11.010
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000453397300043&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/66292
VL  - 842
ER  -
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