Molecular imaging of NF-kappaB in prostate tissue after systemic administration of IL-1β

Abstract

BACKGROUND. Activation of nuclear-factor kappaB (NF-κB) influences the transcription of number of genes, many of which participate in inflammatory responses and tumor development. A wide range of human cancers and inflammatory disorders express inappropriate regulation of NF-κB. The role of NF-κB in intraprostatic inflammation has not been elucidated. METHODS. Using transgenic NF-κB-Luciferase Tag mice coupled to the luciferase reporter gene, we performed serial, noninvasive in vivo and ex vivo molecular imaging of NF-κB activation in the mouse body after systemic administration of mouse pro-inflammatory cytokines: TNF-α, IL-6, and IL-1β at 10 μg/kg body weights. In some experiments, pretreatment with dexamethasone (10 mg/kg) was used to modulate the cytokine-induced NF-κB-dependent luminescence in vivo. RESULTS. Treatment of NF-κB-Luc mice with cytokines increased luminescence in a time- and organ- specific manner. Highest levels of NF-κB-dependent luminescence were observed approximately 3-4 hr after IL-1β administration. An important finding was the cumulative effect of IL-1β to activate NF-κB in the prostate during chronic administration. CONCLUSIONS. The molecular imaging of NF-κB activity might be an attractive approach to distinguish the role of cytokine-induced NF-κB signaling in intraprostatic inflammation and prostate cancer development. Since dexamethasone, a known NF-κB inhibitor, could reduce the IL-1β-induced NF-κB-dependent luminescence in the prostate, NF-κB-Luc mice might be useful tool to screen potential candidate drugs for treatment of inflammation and tumor associated with aberrant NF-κB activity. © 2007 Wiley-Liss, Inc.