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Interferon-gamma synergises with tumour necrosis factor and lymphotoxin-alpha to enhance the mRNA and protein expression of adhesion molecules in mouse brain endothelial cells.

Abstract
Changes to the cerebral microvasculature are evident during cerebral malaria (CM). Activation of the endothelium is likely to be due to the actions of cytokines, circulating levels of which are elevated during CM. Endothelial cells are known to up-regulate the expression of cellular adhesion molecules, which can lead to cellular sequestration and obstruction of vessels. However, it is unknown whether cytokines synergise in the up-regulation of the adhesion molecules involved in CM. In this study, the mRNA and/or protein expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin and E-Selectin were examined in a mouse brain endothelial cell line. Endothelial cells were stimulated with interferon-gamma (IFN-gamma), tumour necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha), alone or in combination. The expression of ICAM-1, VCAM-1, P-selectin and E-Selectin mRNA in mouse brain endothelial cells by TNF and/or LT-alpha was found to be significantly enhanced in the presence of IFN-gamma. The same synergistic effect was found when analyzing ICAM-1 protein expression in cytokine stimulated mouse brain endothelial cells. The findings show that cytokines can synergise to influence gene expression and protein expression in a mouse brain endothelial cell line.
AuthorsSilvia Weiser, Jenny Miu, Helen J Ball, Nicholas H Hunt
JournalCytokine (Cytokine) Vol. 37 Issue 1 Pg. 84-91 (Jan 2007) ISSN: 1043-4666 [Print] England
PMID17412608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Adhesion Molecules
  • Lymphotoxin-alpha
  • RNA, Messenger
  • Tumor Necrosis Factors
  • Interferon-gamma
Topics
  • Animals
  • Brain (drug effects, metabolism)
  • Cell Adhesion Molecules (biosynthesis, genetics)
  • Cell Line
  • Endothelial Cells (drug effects, metabolism)
  • Gene Expression Regulation (drug effects)
  • Interferon-gamma (pharmacology)
  • Lymphotoxin-alpha (pharmacology)
  • Mice
  • RNA, Messenger (genetics, metabolism)
  • Tumor Necrosis Factors (pharmacology)

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