Sphingosylphosphorylcholine is a proinflammatory mediator in cerebral arteries

Christiane Wirrig, Irene Hunter, Fiona A. Mathieson, Graeme F. Nixon (Corresponding Author)

Research output: Contribution to journalArticle

15 Citations (Scopus)

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-¿B 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.
Original languageEnglish
Pages (from-to)212-221
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number1
Early online date16 Jun 2010
DOIs
Publication statusPublished - Jan 2011

Keywords

  • cerebral artery
  • inflammation
  • sphingolipid
  • vasospasm

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