Abstract
Inflammation in de-endothelialized arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor- (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease.
Original language | English |
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Pages (from-to) | 43-50 |
Number of pages | 8 |
Journal | Biochemical Pharmacology |
Volume | 115 |
Early online date | 8 Jul 2016 |
DOIs | |
Publication status | Published - 1 Sep 2016 |
Keywords
- Vascular smooth muscle
- Sphingolipids
- Macrophage
- Nitric oxide synthase
- Lipid raft
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Profiles
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Graeme Nixon
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Personal Chair
- Clinical Medicine
- Institute of Medical Sciences
Person: Academic
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Heather Wilson
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Immunology
- Clinical Medicine
- Institute of Medical Sciences
Person: Academic