Effect of Steroid Administration Ex Vivo on the IkappaB/NF-kappaB Pathway in Human Peripheral Blood Monocytes / 결핵

ABSTRACT

BACKGROUND: Synthetic glucocorticoids are widely used in many chronic inflammatory diseases because of their excellent anti-inflammatory activity. Enhancing the transcription of IkappaB and preventing activated NF-kappaB from binding to kappaB sites are thought to be the underlying mechanisms. But these data are largely derived from in vitro studies using cell lines. In this study, after administrating a steroid to volunteers, we evaluated the effect on the NF-kappaB system. METHODS: Prednisolone(0.5mg/kg/d) was orally administered to 5 healthy volunteers for 7 days. Before and after the administration, we sampled their peripheral blood monocytes, and performed western blot analysis both with stimulation, using IL-1beta, LPS, TNF, and without stimulation(baseline). We also performed EMSA after stimulation with LPS. RESULTS: After ingestion of the steroid, baseline expressions of I(kappa)B(alpha) were increased in two of the subjects, while suppressed degradations of I(kappa)B(alpha) to stimulations were observed in all five. In addition, the binding capacity of NF-kappaB after the administration was decreased. CONCLUSION: Steroid plays such roles as enhancing the transcription of I(kappa)B(alpha), suppressing the DNA binding capacity of NF-kappaB, and suppressing the degradation of I(kappa)B(alpha).