Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways
<p>Abstract</p> <p>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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-10-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://www.journal-inflammation.com/content/2/1/10 |
| _version_ | 1818790602717790208 |
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| author | Sambucetti Lidia C Zhu Lingyun Ahsan Muhammad H Zhang Ning Purchio Anthony F West David B |
| author_facet | Sambucetti Lidia C Zhu Lingyun Ahsan Muhammad H Zhang Ning Purchio Anthony F West David B |
| author_sort | Sambucetti Lidia C |
| collection | DOAJ |
| description | <p>Abstract</p> <p>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 <it>in vivo </it>IκBα expression by imaging <it>I</it>κ<it>B</it>α-<it>luc </it>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 <it>I</it>κ<it>B</it>α-<it>luc </it>transgenic mice are useful for analyzing IκBα expression and the NF-κB transcriptional activity <it>in vivo</it>.</p> |
| first_indexed | 2024-12-18T14:58:04Z |
| format | Article |
| id | doaj.art-4c54c7259ee64b97875ad65991d2c1f3 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-18T14:58:04Z |
| publishDate | 2005-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-4c54c7259ee64b97875ad65991d2c1f32022-12-21T21:03:59ZengBMCJournal of Inflammation1476-92552005-10-01211010.1186/1476-9255-2-10Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathwaysSambucetti Lidia CZhu LingyunAhsan Muhammad HZhang NingPurchio Anthony FWest David B<p>Abstract</p> <p>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 <it>in vivo </it>IκBα expression by imaging <it>I</it>κ<it>B</it>α-<it>luc </it>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 <it>I</it>κ<it>B</it>α-<it>luc </it>transgenic mice are useful for analyzing IκBα expression and the NF-κB transcriptional activity <it>in vivo</it>.</p>http://www.journal-inflammation.com/content/2/1/10IkappaBNF-κBMAP kinasebortezomiblipopolysaccharidebioluminescent imaging |
| spellingShingle | Sambucetti Lidia C Zhu Lingyun Ahsan Muhammad H Zhang Ning Purchio Anthony F West David B Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways Journal of Inflammation IkappaB NF-κB MAP kinase bortezomib lipopolysaccharide bioluminescent imaging |
| title | Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways |
| title_full | Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways |
| title_fullStr | Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways |
| title_full_unstemmed | Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways |
| title_short | Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways |
| title_sort | regulation of iκbα expression involves both nf κb and the map kinase signaling pathways |
| topic | IkappaB NF-κB MAP kinase bortezomib lipopolysaccharide bioluminescent imaging |
| url | http://www.journal-inflammation.com/content/2/1/10 |
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