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- Title
Regulation of IκBα expression involves both NF-#x03BA;B and the MAP kinase signaling pathways.
- Authors
Ning Zhang; Ahsan, Muhammad H.; Lingyun Zhu; Sambucetti, Lidia C.; Purchio, Anthony F.; West, David B.
- Abstract
IκBα is an inhibitor of the nuclear transcription factor NF-κB. Binding of IκBα to NF-κB inactivates the transcriptional activity of NF-κB. Expression of IκBα itself is regulated by NF-κB, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo IκBα expression by imaging IκBα-luc transgenic mice for IκBα promoter driven luciferase activity. We demonstrated a rapid and systemic induction of IκBα expression in the transgenic mice following treatment with LPS. The induction was high in liver, spleen, lung and intestine and lower in the kidney, heart and brain. The luciferase induction in the liver correlated with increased IκBα mRNA level. Pre-treatment with proteasome inhibitor bortezomib dramatically suppressed LPSinduced luciferase activity. The p38 kinase inhibitor SB203580 also showed moderate inhibition of LPS-induced luciferase activity. Analysis of IκBα mRNA in the liver tissue showed a surprising increase of the IκBα mRNA after bortezomib and SB203580 treatments, which could be due to increased IκBα mRNA stability. Our data demonstrate that regulation of IκBα expression involves both the NF-κB and the p38 signaling pathways. The IκBα-luc transgenic mice are useful for analyzing IκBα expression and the NF-κB transcriptional activity in vivo.
- Subjects
TRANSCRIPTION factors; NUCLEAR receptors (Biochemistry); GENETIC regulation; LUCIFERASES; TRANSGENIC mice; LABORATORY mice
- Publication
Journal of Inflammation, 2005, Vol 2, p10
- ISSN
1476-9255
- Publication type
Article
- DOI
10.1186/1476-9255-2-10