Nuclear factor κB nuclear translocation as a crucial marker of brain response to interleukin‐1. A study in rat and interleukin‐1 type I deficient mouse

• Published in: Journal of neurochemistry Vol. 87; no. 4; pp. 1024 - 1036
• Main Authors: Nadjar, Agnès, Combe, Chantal, Layé, Sophie, Tridon, Viviane, Dantzer, Robert, Amédée, Thierry, Parnet, Patricia
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2003
• Subjects: brain; cytokine receptors; interleukin‐1β; neuroimmunology; nuclear factor κB
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.02097.x

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‐1β to its specific receptor interleukin‐1 receptor type I (IL‐1RI) leads to nuclear factor kappa B (ΝFκB) nuclear translocation and a robust transcriptional activation of inhibitor of kappa B alpha (IκBα) 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‐NFκB translocation induced by peripheral injection of IL‐1β. Moreover, it has been previously shown that monitoring IκBα mRNA synthesis is an effective tool to investigate the activity of the transcription factor NFκB into the CNS. However in the present study we observed time‐related and cell‐type differences between IκBα mRNA synthesis and p65‐NFκB translocation. This indicates that the expression of IκBα mRNA does not strictly parallel p65‐NFκB nuclear translocation, suggesting that these markers are not interchangeable to investigate NFκB activity but must be studied together. Thus, we hypothesize that IL‐1β reached the brain across the CVOs that lack a BBB and endothelial cells all over the brain and interacted with its receptors to induce NFκB translocation. The study of the consequences of the impairment of NFκB pathway activation in in vivo experimentation should bring important clues about the precise role of this transcription factor.