Localization of interleukin-1 beta 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.
Interleukin (IL)-1 beta-converting enzyme (ICE) cleaves the biologically inactive precursor form of IL-1 beta into mature, bioactive IL-1 beta. Because of the potent effects of IL-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-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), 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-1ra might be an endogenous vascular protective agent.
Wong
M L
ML
Clinical Neuroendocrinology Branch, National Institute of Mental Health, NIH, Bethesda, Md 20892-1284, USA.
Bongiorno
P B
PB
Gold
P W
PW
Licinio
J
J
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001808:Blood Vessels / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply*; D020170:Caspase 1; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011453:Prostaglandins; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D009569:Nitric Oxide; D003546:Cysteine Endopeptidases; D020170:Caspase 1