Regulation of I[kappa]B alpha expression involves both NF-[kappa]B and the MAP kinase signaling pathways

I[kappa]B alpha is an inhibitor of the nuclear transcription factor NF-[kappa]B. Binding of I[kappa]B alpha to NF-[kappa]B inactivates the transcriptional activity of NF-[kappa]B. Expression of I[kappa]B alpha itself is regulated by NF-[kappa]B, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo I[kappa]B alpha expression by imaging I[kappa]B alpha -luc transgenic mice for I[kappa]B alpha promoter driven luciferase activity. We demonstrated a rapid and systemic induction of I[kappa]B alpha 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 I[kappa]B alpha mRNA level. Pre-treatment with proteasome inhibitor bortezomib dramatically suppressed LPS-induced luciferase activity. The p38 kinase inhibitor SB203580 also showed moderate inhibition of LPS-induced luciferase activity. Analysis of I[kappa]B alpha mRNA in the liver tissue showed a surprising increase of the I[kappa]B alpha mRNA after bortezomib and SB203580 treatments, which could be due to increased I[kappa]B alpha mRNA stability. Our data demonstrate that regulation of I[kappa]B alpha expression involves both the NF-[kappa]B and the p38 signaling pathways. The I[kappa]B alpha -luc transgenic mice are useful for analyzing I[kappa]B alpha expression and the NF-[kappa]B transcriptional activity in vivo.