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  • Title: Molecular imaging of NF-kappaB in prostate tissue after systemic administration of IL-1 beta.
    Author: Vykhovanets EV, Shukla S, MacLennan GT, Resnick MI, Carlsen H, Blomhoff R, Gupta S.
    Journal: Prostate; 2008 Jan 01; 68(1):34-41. PubMed ID: 18004768.
    Abstract:
    BACKGROUND: Activation of nuclear-factor kappaB (NF-kappaB) 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-kappaB. The role of NF-kappaB in intraprostatic inflammation has not been elucidated. METHODS: Using transgenic NF-kappaB-Luciferase Tag mice coupled to the luciferase reporter gene, we performed serial, noninvasive in vivo and ex vivo molecular imaging of NF-kappaB activation in the mouse body after systemic administration of mouse pro-inflammatory cytokines: TNF-alpha, IL-6, and IL-1 beta at 10 microg/kg body weights. In some experiments, pretreatment with dexamethasone (10 mg/kg) was used to modulate the cytokine-induced NF-kappaB-dependent luminescence in vivo. RESULTS: Treatment of NF-kappaB-Luc mice with cytokines increased luminescence in a time- and organ- specific manner. Highest levels of NF-kappaB-dependent luminescence were observed approximately 3-4 hr after IL-1 beta administration. An important finding was the cumulative effect of IL-1 beta to activate NF-kappaB in the prostate during chronic administration. CONCLUSIONS: The molecular imaging of NF-kappaB activity might be an attractive approach to distinguish the role of cytokine-induced NF-kappaB signaling in intraprostatic inflammation and prostate cancer development. Since dexamethasone, a known NF-kappaB inhibitor, could reduce the IL-1 beta-induced NF-kappaB-dependent luminescence in the prostate, NF-kappaB-Luc mice might be useful tool to screen potential candidate drugs for treatment of inflammation and tumor associated with aberrant NF-kappaB activity.
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