Document Detail


A robust in vitro screening assay to identify NF-kappaB inhibitors for inflammatory muscle diseases.
MedLine Citation:
PMID:  19596085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Specific therapies are not available for inflammatory muscle diseases. We and others have shown that the pro-inflammatory NF-kappaB pathway is highly activated in these conditions. Since NF-kappaB is an important therapeutic target, we decided to utilize an in vitro screening assay to identify potential inhibitors that block TNF-alpha induced NF-kappaB activation in a C2C12 muscle line stably expressing an NF-kappaB luciferase reporter gene. Upon evaluation of multiple anti-inflammatory agents in undifferentiated myoblasts as well as differentiated myotubes , we found different levels of inhibition depending on the state of differentiation. Interestingly, we found that some drugs that are known to inhibit NF-kappaB in immune cells were not effective in muscle cells. Drug toxicity was assessed for using an MTT cell viability assay, and the validity of the luciferase assay was verified by immunostaining for NF-kappaB nuclear translocation in myoblasts. In conclusion, we have determined the optimal assay conditions for detecting potentially valuable NF-kappaB inhibitors for the first time in a muscle cell line that may have significant therapeutic potential for inflammatory muscle diseases.
Authors:
Andreas R Baudy; Nandita Saxena; Heather Gordish; Eric P Hoffman; Kanneboyina Nagaraju
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-07-21
Journal Detail:
Title:  International immunopharmacology     Volume:  9     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-28     Completed Date:  2010-03-01     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1209-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors / pharmacology*
Mice
Muscle, Skeletal / drug effects*,  immunology,  metabolism,  pathology
Myositis / drug therapy*,  immunology,  pathology
NF-kappa B / antagonists & inhibitors*
Reproducibility of Results
Signal Transduction / drug effects,  immunology
Tumor Necrosis Factor-alpha / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
5U54HD053177/HD/NICHD NIH HHS; K26 OD011171/OD/NIH HHS; K26 RR032082/RR/NCRR NIH HHS; R01 AR050478/AR/NIAMS NIH HHS; R01 AR050478-06/AR/NIAMS NIH HHS; R01-AR050478/AR/NIAMS NIH HHS; R01-NS029525/NS/NINDS NIH HHS; U54 HD053177/HD/NICHD NIH HHS; U54 HD053177-04/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/NF-kappa B; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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