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

Abstract

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

High‐fat diet increases NF‐κB signaling in the prostate of reporter mice

“…Imaging of transgenic mice was performed according to our previous publication [29]. The images of mice were taken after each time interval of feeding.…”

“…The images of mice were taken after each time interval of feeding. The transgenic mice NF-κB-dependent luciferase activity both in vivo and ex vivo was measured as described previously with some modifications [29]. …”

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

“…Vykhovanets et al, 2008, showed that the administration of TNF- α , IL-6, or IL-1 β induces the activation of NF- κ B in the prostate and that Dexamethasone could downmodulate the activation of the NF- κ B cytokine [46]. A similar result has been showed in an ulcerative colitis model in which Dexamethasone increased the expression of IL-4 [47].…”

Cytokine Effects on Cell Viability and Death of Prostate Carcinoma Cells

“…A previous study has shown that IL-1 β activates NF- κ B in LNCaP cells on the basis of a significant increase of phosphorylated NF- κ B in LNCaP cells treated with IL-1 β in comparison to control untreated cells [17]. Moreover, IL-1 β activates NF- κ B in prostate tissue in mouse models [48, 49]. Since NF- κ B activation proceeds through ubiquitination and degradation of the I κ B- α protein [11, 12, 27, 32], reduced levels of I κ B- α protein indicate NF- κ B activation.…”