Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease

Fabian Cordts, Stuart Pitson, Christoph Tabeling, Ian Gibbins, David Moffat, Hubertus Jersmann, Sandra Hodge, Rainer Haberberger

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    AbstractAims 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). Main methods 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. Key findings 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. Significance 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.

    Original languageEnglish
    Pages (from-to)806-811
    Number of pages6
    JournalLife Sciences
    Volume89
    Issue number21-22
    DOIs
    Publication statusPublished - 21 Nov 2011

    Keywords

    • COPD
    • Keywords
    • RT-qPCR
    • S1P
    • S1P receptor 5
    • Sphingosine 1-phosphate
    • Sphingosine kinase activity

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