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- Title
NFκB activates in vivo the synthesis of inducible Cox-2 in the brain.
- Authors
Nadjar, Agnès; Tridon, Viviane; May, Michael J.; Ghosh, Sankar; Dantzer, Robert; Amédée, Thierry; Parnet, Patricia
- Abstract
Interleukin-1β (IL-1β) induces cyclooxygenase-2 (Cox-2) expression in many of its cellular targets resulting in production and release of prostaglandins. Although IL-1β-induced Cox-2 expression most likely requires activation of nuclear transcription factor kappa B (NFκB) pathway, this has never been formally demonstrated in vivo. We tested this using a specific inhibitor of NFκB activation, the NEMO binding domain (NBD) peptide, that has been shown previously to be effective in various in vivo models of acute inflammation. Incubation of rat glioma cells with the NBD peptide blocked IL-1β-induced NFκB nuclear translocation. Furthermore, after injection of a biotinylated version of the NBD peptide into the lateral ventricle of the brain, we found that it readily diffused to its potential cellular targets in vivo. To test the effects of the peptide on NFκB activation and Cox-2 expression in the brain, we injected it intracerebroventricularly (36 μg/rat) into rats before intraperitoneal injection of IL-1β (60 μg/kg). Treatment with NBD peptide completely abolished IL-1β-induced NFκB activation and Cox-2 synthesis in microvasculature. In contrast, the peptide had no effect on constitutive neuronal Cox-2. These findings strongly support the hypothesis that IL-1β-induced NFκB activation plays a major role in transmission of immune signals from the periphery to the brain.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1047–1059. doi:10.1038/sj.jcbfm.9600106; published online 9 March 2005
- Subjects
BLOOD vessels; CYCLOOXYGENASE 2; CENTRAL nervous system depressants; INTERLEUKIN-1; RESEARCH
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2005, Vol 25, Issue 8, p1047
- ISSN
0271-678X
- Publication type
Article
- DOI
10.1038/sj.jcbfm.9600106