Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/68474
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Type: Journal article
Title: Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease
Author: Cordts, F.
Pitson, S.
Tabeling, C.
Gibbins, I.
Moffat, D.
Jersmann, H.
Hodge, S.
Haberberger, R.
Citation: Life Sciences, 2011; 89(21-22):806-811
Publisher: Pergamon-Elsevier Science Ltd
Issue Date: 2011
ISSN: 0024-3205
1879-0631
Statement of
Responsibility: 
Fabian Cordts, Stuart Pitson, Christoph Tabeling, Ian Gibbins, David F. Moffat, Hubertus Jersmann, Sandra Hodge, Rainer V. Haberberger
Abstract: <h4>Aims</h4>Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Despite its importance, treatment methods are limited and restricted to symptomatic care, highlighting the urgent need for new treatment options. Tissue damage in COPD is thought to result from an inability of the normal repair processes with accumulation of apoptotic material and impaired clearance of this material by macrophages in the airways. Lung inflammation involves the bioactive sphingolipid sphingosine 1-phosphate (S1P).<h4>Main methods</h4>We investigated lung tissue samples from 55 patients (25 with COPD) undergoing lobectomies for management of cancer. We analysed the sphingosine-kinase (SphK) mRNA expression profile, SphK enzyme activity as well as the localisation and expression of individual proteins related to the SphK-signalling system.<h4>Key findings</h4>We show in this study for the first time a comprehensive expression profile of all synthesising enzymes, receptors and degrading enzymes of the SphK-signalling system in the human lung. Multivariate ANOVA showed that the relative mRNA expression of S1P receptor (S1PR) subtype 5 was reduced in COPD. There were strong positive correlations between the mRNA expression of S1PR5 and S1PR1 and S1PR3, and between S1PR3 and S1PR2. A significant negative correlation was found between S1PR1 and SphK protein activity.<h4>Significance</h4>The correlations between expression levels of receptors and enzymes involved in the sphingosine kinase signalling system in the lung suggest common regulatory mechanisms. Our findings of reduced S1PR5 in COPD and the correlation with other S1P receptors in COPD identify S1PR5 as a possible novel target for pharmacotherapy.
Keywords: COPD
RT-qPCR
Sphingosine 1-phosphate
S1P
Sphingosine kinase activity
S1P receptor 5
Rights: Copyright © 2011 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.lfs.2011.08.018
Grant ID: NHMRC
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