title: Sphingosylphosphorylcholine is a proinflammatory mediator in cerebral arteries.
abstract: Inflammation has an important function in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH); however, the mediators of this inflammatory response have not been clearly identified. In this study, we have investigated the potential function of two sphingolipids, which occur naturally in plasma and serum, sphingosylphosphorylcholine (SPC) and sphingosine 1-phosphate (S1P), to act as proinflammatory mediators in cerebral artery vascular smooth muscle (VSM) cells. In rat cerebral arteries, SPC but not S1P activated p38 mitogen-activated protein kinase (MAPK). Using transcription factor arrays, two proinflammatory transcription factors activated by SPC in cerebral arteries were identified--nuclear factor-κB and CCAAT-enhancer-binding protein. Both these transcription factors were activated by SPC in a p38MAPK-dependent manner. To determine whether this contributed to vascular inflammation, an inflammatory protein array was performed, which showed that SPC increased release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured rat VSM cells. This increase in MCP-1 expression was confirmed in cerebral arteries. The S1P did not increase MCP-1 release. Taken together, our results suggest that SPC, but not S1P, can act as a proinflammatory mediator in cerebral arteries. This may contribute to inflammation observed after SAH and may be part of the initiating event in vasospasm.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wirrig
authors.forename: Irene
authors.initials: I
authors.lastname: Hunter
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Mathieson
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation; D020301:Vasospasm, Intracranial / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D008246:Lysophospholipids; D016328:NF-kappa B; D014157:Transcription Factors; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C060506:sphingosine 1-phosphate; D048051:p38 Mitogen-Activated Protein Kinases; D013110:Sphingosine