Nuclear factor kappaB nuclear translocation as a crucial marker of brain response to interleukin-1. A study in rat and interleukin-1 type I deficient mouse.
The signalling pathways that mediate early central effects of interleukin-1 (IL-1) during the acute phase reaction have been poorly elucidated. Interaction of IL-1beta to its specific receptor interleukin-1 receptor type I (IL-1RI) leads to nuclear factor kappa B (NuFkappaB) nuclear translocation and a robust transcriptional activation of inhibitor of kappa B alpha (IkappaBalpha) within the rat brain. Indeed, we demonstrated that IL-1RI expressed in blood brain barrier (BBB) cells and in circumventricular organs (CVOs) is crucial for p65-NFkappaB translocation induced by peripheral injection of IL-1beta. Moreover, it has been previously shown that monitoring IkappaBalpha mRNA synthesis is an effective tool to investigate the activity of the transcription factor NFkappaB into the CNS. However in the present study we observed time-related and cell-type differences between IkappaBalpha mRNA synthesis and p65-NFkappaB translocation. This indicates that the expression of IkappaBalpha mRNA does not strictly parallel p65-NFkappaB nuclear translocation, suggesting that these markers are not interchangeable to investigate NFkappaB activity but must be studied together. Thus, we hypothesize that IL-1beta reached the brain across the CVOs that lack a BBB and endothelial cells all over the brain and interacted with its receptors to induce NFkappaB translocation. The study of the consequences of the impairment of NFkappaB pathway activation in in vivo experimentation should bring important clues about the precise role of this transcription factor.
Nadjar
Agnès
A
INRA-INSERM U.394, Institut F Magendie, Bordeaux, France.
Combe
Chantal
C
Layé
Sophie
S
Tridon
Viviane
V
Dantzer
Robert
R
Amédée
Thierry
T
Parnet
Patricia
P
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology / Q000502:physiology
D015415:Biomarkers; D020672:I-kappa B Proteins; D007375:Interleukin-1; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D000072000:NF-KappaB Inhibitor alpha