Effect on NF-κB and Associated Cytokines After Being Chronically Injected With Pyrrolidine Dithiocarbamate (PDTC) Using the MDX Mouse Model
Gregory W. Millman
Dr. John J. Rutter and Dr. C. George Carlson (AT Still University), Faculty Mentors
Previous experiments indicate that chronic inhibition of the NF-κB pathway is beneficial in treating the mdx mouse, a model for Duchenne muscular dystrophy (Carlson et al., Neurobiology of Disease, 20, 719, 2005; Messina et al., Exper. Neurol.,198, 234, 2006). In the present experiments, we further examined the potential influence of the NF-κB pathway on dystrophic pathogenesis. Chronic treatment with PDTC (50 mg/kg), an inhibitor of the NF-κB pathway, produced a decrease in total cellular NF-κB and decreased the nuclear activation. Untreated mdx costal and crural diaphragms exhibited higher cytosolic levels of three NF-κB-dependent cytokines (IL-1β: crural diaphragm, p=.040; costal diaphragm, p=.039; TNF-α: costal diaphragm, p=.040; IL-6: costal diaphragm, p=.216; crural p=.054). These results are consistent with the hypothesis that the NF-κB pathway exerts a pathogenic influence on the dystrophic phenotype.
Keywords: NF-κB, mdx mouse, DMD, TNF-α, IL-1β, IL-6, PDTC
Topic(s):Biology
Presentation Type: Oral Paper
Session: 27-3
Location: VH 1408
Time: 10:15