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Regulation of IkappaBalpha expression involves both NF-kappaB and the MAP kinase signaling pathways.

Abstract：

:IkappaBalpha is an inhibitor of the nuclear transcription factor NF-kappaB. Binding of IkappaBalpha to NF-kappaB inactivates the transcriptional activity of NF-kappaB. Expression of IkappaBalpha itself is regulated by NF-kappaB, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo IkappaBalpha expression by imaging IkappaBalpha-luc transgenic mice for IkappaBalpha promoter driven luciferase activity. We demonstrated a rapid and systemic induction of IkappaBalpha 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 IkappaBalpha 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 IkappaBalpha mRNA in the liver tissue showed a surprising increase of the IkappaBalpha mRNA after bortezomib and SB203580 treatments, which could be due to increased IkappaBalpha mRNA stability. Our data demonstrate that regulation of IkappaBalpha expression involves both the NF-kappaB and the p38 signaling pathways. The IkappaBalpha-luc transgenic mice are useful for analyzing IkappaBalpha expression and the NF-kappaB transcriptional activity in vivo.

journal_name

J Inflamm (Lond)

journal_title

Journal of inflammation (London, England)

authors

Zhang N,Ahsan MH,Zhu L,Sambucetti LC,Purchio AF,West DB

doi

10.1186/1476-9255-2-10

keywords:

subject

Has Abstract

pub_date

2005-10-05 00:00:00

pages

10

issn

1476-9255

pii

1476-9255-2-10

journal_volume

2

pub_type

杂志文章

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