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Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8

NF-κB activation is a critical signaling event in the inflammatory response and has been implicated in a number of pathological lung diseases. To enable the assessment of NF-κB activity in the lungs, we transfected a luciferase based NF-κB reporter into the lungs of mice or into Raw264.7 cells in cu...

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Autores principales: Ansaldi, Dan, Hod, Eldad A., Stellari, Fabio, Kim, Jae-Beom, Lim, Ed, Roskey, Mark, Francis, Kevin P., Singh, Rajendra, Zhang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178604/
https://www.ncbi.nlm.nih.gov/pubmed/21966423
http://dx.doi.org/10.1371/journal.pone.0025093
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author Ansaldi, Dan
Hod, Eldad A.
Stellari, Fabio
Kim, Jae-Beom
Lim, Ed
Roskey, Mark
Francis, Kevin P.
Singh, Rajendra
Zhang, Ning
author_facet Ansaldi, Dan
Hod, Eldad A.
Stellari, Fabio
Kim, Jae-Beom
Lim, Ed
Roskey, Mark
Francis, Kevin P.
Singh, Rajendra
Zhang, Ning
author_sort Ansaldi, Dan
collection PubMed
description NF-κB activation is a critical signaling event in the inflammatory response and has been implicated in a number of pathological lung diseases. To enable the assessment of NF-κB activity in the lungs, we transfected a luciferase based NF-κB reporter into the lungs of mice or into Raw264.7 cells in culture. The transfected mice showed specific luciferase expression in the pulmonary tissues. Using these mouse models, we studied the kinetics of NF-κB activation following exposure to lipopolysaccharide (LPS). The Raw264.7 cells expressed a dose-dependent increase in luciferase following exposure to LPS and the NF-κB reporter mice expressed luciferase in the lungs following LPS challenge, establishing that bioluminescence imaging provides adequate sensitivity for tracking the NF-κB activation pathway. Interventions affecting the NF-κB pathway are promising clinical therapeutics, thus we further examined the effect of IKK-2 inhibition by MLN120B and glycogen synthase kinase 3 beta inhibition by TDZD-8 on NF-κB activation. Pre-treatment with either MLN120B or TDZD-8 attenuated NF-κB activation in the pulmonary tissues, which was accompanied with suppression of pro-inflammatory chemokine MIP-1ß and induction of anti-inflammatory cytokine IL-10. In summary, we have established an imaging based approach for non-invasive and longitudinal assessment of NF-κB activation and regulation during acute lung injury. This approach will potentiate further studies on NF-κB regulation under various inflammatory conditions.
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spelling pubmed-31786042011-09-30 Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8 Ansaldi, Dan Hod, Eldad A. Stellari, Fabio Kim, Jae-Beom Lim, Ed Roskey, Mark Francis, Kevin P. Singh, Rajendra Zhang, Ning PLoS One Research Article NF-κB activation is a critical signaling event in the inflammatory response and has been implicated in a number of pathological lung diseases. To enable the assessment of NF-κB activity in the lungs, we transfected a luciferase based NF-κB reporter into the lungs of mice or into Raw264.7 cells in culture. The transfected mice showed specific luciferase expression in the pulmonary tissues. Using these mouse models, we studied the kinetics of NF-κB activation following exposure to lipopolysaccharide (LPS). The Raw264.7 cells expressed a dose-dependent increase in luciferase following exposure to LPS and the NF-κB reporter mice expressed luciferase in the lungs following LPS challenge, establishing that bioluminescence imaging provides adequate sensitivity for tracking the NF-κB activation pathway. Interventions affecting the NF-κB pathway are promising clinical therapeutics, thus we further examined the effect of IKK-2 inhibition by MLN120B and glycogen synthase kinase 3 beta inhibition by TDZD-8 on NF-κB activation. Pre-treatment with either MLN120B or TDZD-8 attenuated NF-κB activation in the pulmonary tissues, which was accompanied with suppression of pro-inflammatory chemokine MIP-1ß and induction of anti-inflammatory cytokine IL-10. In summary, we have established an imaging based approach for non-invasive and longitudinal assessment of NF-κB activation and regulation during acute lung injury. This approach will potentiate further studies on NF-κB regulation under various inflammatory conditions. Public Library of Science 2011-09-22 /pmc/articles/PMC3178604/ /pubmed/21966423 http://dx.doi.org/10.1371/journal.pone.0025093 Text en Ansaldi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ansaldi, Dan
Hod, Eldad A.
Stellari, Fabio
Kim, Jae-Beom
Lim, Ed
Roskey, Mark
Francis, Kevin P.
Singh, Rajendra
Zhang, Ning
Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title_full Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title_fullStr Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title_full_unstemmed Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title_short Imaging Pulmonary NF-kappaB Activation and Therapeutic Effects of MLN120B and TDZD-8
title_sort imaging pulmonary nf-kappab activation and therapeutic effects of mln120b and tdzd-8
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178604/
https://www.ncbi.nlm.nih.gov/pubmed/21966423
http://dx.doi.org/10.1371/journal.pone.0025093
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