Decreased Exercise-Induced Expression of Nuclear Factor-{kappa}B-Regulated Genes in Muscle of Patients With COPD.

ABSTRACT BACKGROUND: NF-kappaB activation and oxidative stress are physiological responses of skeletal muscle to exercise but may be impaired in COPD patients. Therefore, we investigated NF-kappaB activity and expression of NF-kappaB regulated genes in muscle of COPD patients and controls before and after exercise. METHODS: Quadriceps specimens were obtained before, immediately and 2h after a submaximal cycle ergometry test from 7 COPD patients (50.6 +/- 5.7 SEM) and 7 age-matched controls. NF-kappaB DNA binding activity in muscle and peripheral blood mononuclear cells (PBMCs) was determined using electrophoretic mobility shift assay and ELISA respectively. mRNA expression and protein carbonylation were measured by RT-PCR and Western blot, respectively. RESULTS: In controls, IL-6, IkappaBalpha, TNF-alpha, IL-1beta, superoxide dismutase, thioredoxin, heme oxygenase 1 and heat shock protein70 were upregulated in muscle after exercise, whereas in COPD only IL-6 mRNA was increased. Exercise-induced anti-apoptotic Bcl2 mRNA levels were attenuated in COPD compared to controls. Basal muscle protein oxidation was higher in COPD than in controls, but attenuated in response to exercise. No exercise-induced changes in NF-kappaB DNA binding activity in muscle and PBMCs of both groups were detected. CONCLUSIONS: Skeletal muscle of COPD patients is characterized by an impaired response to exercise of NF-kappaB regulated genes encoding inflammatory cytokines, antioxidants, stress proteins and survival factors.