Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways

Journal of Inflammation

David B West¹  Anthony F Purchio¹  Lidia C Sambucetti¹  Lingyun Zhu¹  Muhammad H Ahsan¹  Ning Zhang¹ 

[1] Xenogen Corporation, 860 Atlantic Avenue, Alameda, California 94501, USA

关键词: bioluminescent imaging;    lipopolysaccharide;    bortezomib;    MAP kinase;    NF-κB;    IkappaB;   

Others  :  826717
DOI  :  10.1186/1476-9255-2-10

 received in 2005-03-24, accepted in 2005-10-05,  发布年份 2005

【 摘 要 】

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 LPS-induced 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.

【 授权许可】

   
2005 Zhang et al; licensee BioMed Central Ltd.

【 图 表 】

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