Imperial College London
Alternate

Professor Kazuhiro Ito

Faculty of Medicine, National Heart & Lung Institute

Principal Research Fellow in Respiratory Molecular Pharmacol
 
 
 
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Contact

 

+44 (0)20 7594 0953k.ito Website

 
 
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Location

 

412Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Coates:2021:10.1371/journal.pone.0246050,
author = {Coates, M and Alton, E and Rapeport, W and Davies, J and Ito, K},
doi = {10.1371/journal.pone.0246050},
journal = {PLoS One},
title = {Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway},
url = {http://dx.doi.org/10.1371/journal.pone.0246050},
volume = {16},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pseudomonas aeruginosa (Pa) infection is a major cause of airway inflammation in immunocompromised and cystic fibrosis (CF) patients. Mitogen-activated protein (MAP) and tyrosine kinases are integral to inflammatory responses and are therefore potential targets for novel anti-inflammatory therapies. We have determined the involvement of specific kinases in Pa-induced inflammation. The effects of kinase inhibitors against p38MAPK, MEK 1/2, JNK 1/2, Syk or c-Src, a combination of a p38MAPK with Syk inhibitor, or a novel narrow spectrum kinase inhibitor (NSKI), were evaluated against the release of the proinflammatory cytokine/chemokine, IL-6 and CXCL8 from BEAS-2B and CFBE41o- epithelial cells by Pa. Effects of a Syk inhibitor against phosphorylation of the MAPKs were also evaluated. IL-6 and CXCL8 release by Pa were significantly inhibited by p38MAPK and Syk inhibitors (p<0.05). Phosphorylation of HSP27, but not ERK or JNK, was significantly inhibited by Syk kinase inhibition. A combination of p38MAPK and Syk inhibitors showed synergy against IL-6 and CXCL8 induction and an NSKI completely inhibited IL-6 and CXCL8 at low concentrations. Pa-induced inflammation is dependent on p38MAPK primarily, and Syk partially, which is upstream of p38MAPK. The NSKI suggests that inhibiting specific combinations of kinases is a potent potential therapy for Pa-induced inflammation.
AU  - Coates,M
AU  - Alton,E
AU  - Rapeport,W
AU  - Davies,J
AU  - Ito,K
DO  - 10.1371/journal.pone.0246050
PY  - 2021///
SN  - 1932-6203
TI  - Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway
T2  - PLoS One
UR  - http://dx.doi.org/10.1371/journal.pone.0246050
UR  - http://hdl.handle.net/10044/1/87163
VL  - 16
ER  -
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