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

14 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

Fingerprint

Cerebral Arteries
Chemokine CCL2
Transcription Factors
Subarachnoid Hemorrhage
Inflammation
Vascular Smooth Muscle
Smooth Muscle Myocytes
CCAAT-Enhancer-Binding Proteins
Intracranial Vasospasm
Protein Array Analysis
Sphingolipids
p38 Mitogen-Activated Protein Kinases
Chemokines
Blood Vessels
sphingosine phosphorylcholine
sphingosine 1-phosphate
Serum

Keywords

  • cerebral artery
  • inflammation
  • sphingolipid
  • vasospasm

Cite this

Sphingosylphosphorylcholine is a proinflammatory mediator in cerebral arteries. / Wirrig, Christiane; Hunter, Irene; Mathieson, Fiona A.; Nixon, Graeme F. (Corresponding Author).

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 1, 01.2011, p. 212-221.

Research output: Contribution to journalArticle

Wirrig, Christiane ; Hunter, Irene ; Mathieson, Fiona A. ; Nixon, Graeme F. / Sphingosylphosphorylcholine is a proinflammatory mediator in cerebral arteries. In: Journal of Cerebral Blood Flow and Metabolism. 2011 ; Vol. 31, No. 1. pp. 212-221.
@article{b109d23c59284a9c95c643ea94f1b691,
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-¿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.",
keywords = "cerebral artery, inflammation, sphingolipid, vasospasm",
author = "Christiane Wirrig and Irene Hunter and Mathieson, {Fiona A.} and Nixon, {Graeme F.}",
year = "2011",
month = "1",
doi = "10.1038/jcbfm.2010.79",
language = "English",
volume = "31",
pages = "212--221",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Sphingosylphosphorylcholine is a proinflammatory mediator in cerebral arteries

AU - Wirrig, Christiane

AU - Hunter, Irene

AU - Mathieson, Fiona A.

AU - Nixon, Graeme F.

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

KW - cerebral artery

KW - inflammation

KW - sphingolipid

KW - vasospasm

U2 - 10.1038/jcbfm.2010.79

DO - 10.1038/jcbfm.2010.79

M3 - Article

VL - 31

SP - 212

EP - 221

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 1

ER -