Cyclic adenosine monophosphate regulates the expression of the intercellular adhesion molecule and the inducible nitric oxide synthase in brain endothelial cells

Irina V. Balyasnikova, Dale A. Pelligrino, John Greenwood, Peter Adamson, Serge Dragon, Hassan Raza, Elena Galea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The authors studied whether cyclic AMP (cAMP), a widespread regulator of inflammation, modulates the cytokine-mediated expression of the intercellular adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), and the inflammatory nitric oxide synthase 2 (NOS-2), in primary and immortalized brain endothelial cell cultures (GP8.3 cell line). When measured by enzyme- linked immunosorbent assay (ELISA), ICAM-1 was constitutively expressed and was upregulated twofold by interleukin-1β, with no effect of interferon-γ. The NOS-2 activity, assessed by nitrite accumulation, was absent from untreated cultures but was induced by interleukin-1β and interferon-γ acting synergistically. Stimulation of cAMP-dependent pathways with forskolin or dibutyryl cAMP decreased ICAM-1 protein expression, whereas it increased NOS-2 protein expression. For both ICAM-1 and NOS-2, mRNA expression correlated with protein expression. Blockade of NOS activity with L-N- monomethylargiuine (L-NMMA) did not alter ICAM-1 expression, indicating that the nitric oxide released by NOS-2 did not cause the down-regulation of ICAM- 1. Analysis of NFκB activation indicated that cAMP acted through a mechanism other than inhibition of nuclear translocation of NFκB. The authors conclude that cAMP modulates the expression of proinflammatory molecules in brain endothelium. This suggests that inflammatory processes at the blood-brain barrier in vivo may be regulated by perivascular neurotransmitters via cAMP.

Original languageEnglish (US)
Pages (from-to)688-699
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume20
Issue number4
DOIs
StatePublished - 2000

Keywords

  • Adhesion molecule
  • Blood-brain barrier
  • Inflammation
  • Interferon-γ
  • Interleukin-1β
  • L-NMMA
  • NFκB
  • Nitric oxide synthase 2

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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