Localization of interleukin-1β converting enzyme mRNA in rat brain vasculature: Evidence that the genes encoding the interleukin-1 system are constitutively expressed in brain blood vessels: Pathophysiological implications

Ma Li Wong, Peter B. Bongiorno, Philip W. Gold, Julio Licinio

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Interleukin (IL)-1β-convertmg enzyme (ICE) cleaves the biologically inactive precursor form of IL-1β into mature, bioactive IL-1β. Because of the potent effects oflL-1 in blood vessels, we conducted an in situ hybridization study to determine whether ICE mRNA is constitutively expressed in adult rat brain vasculature. Using in situ hybridization histochemistry, we were able to demonstrate that mRNA in blood vessels scattered throughout the brain. In a second set experiments, we found that the genes encoding not only ICE, but also IL-1α, IL-lβ, IL-1 receptor antagonist (IE-Ira), and the IL-1 type I receptor are expressed in brain vasculature. To our knowledge this is the first report documenting the expression of the genes encoding all of the functional elements of the IL-1 system in the same tissue. Our findings have three pathophysiological implications. First, they indicate a possible site where peripheral IL-1 may act in the brain. The vascular IL-1 system stimulates the production of nitric oxide and prostanoids, which could act as mediators of the effects of peripheral IL-1 in the central nervous system. Additionally, vascular IL-1 is known to activate adhesion molecules; our data that the genes encoding the IL-1 system are expressed in brain vasculature further support the concept that IL-1 is implicated in the pathophysiology of atherosclerosis and stroke. Finally, in the context of previous studies documenting that IL-1ra inhibits the effects of IL-1 on endothelial cells, our findings of endogenous IL-1ra mRNA in brain vasculature indicate that IL-lra might be an endogenous vascular protective agent.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalNeuroImmunoModulation
Volume2
Issue number3
DOIs
Publication statusPublished or Issued - 1995

Keywords

  • Brain
  • In situ hybridization
  • Interleukin-1
  • Interleukin-1 receptors
  • lnterleukin-1 converting enzyme
  • Messenger RNA
  • RNA probes
  • Vascular endothelium

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

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