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Molecular imaging of NF-kappaB in prostate tissue after systemic administration of IL-1 beta
Eugene V Vykhovanets1, Sanjeev Shukla, Gregory T MacLennan
1Department of Urology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
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.
Insights
Nuclear-factor kappaB (NF-kappaB) plays a role in inflammation and cancer. This study used NF-kappaB-Luc mice to image NF-kappaB activation in vivo, revealing its role in prostate inflammation and potential for drug screening.
Area of Science:
- Molecular imaging
- Inflammation and Cancer Biology
- Biomedical Research
Background:
- Nuclear-factor kappaB (NF-kappaB) signaling is implicated in inflammatory responses and tumor development, with dysregulation observed in various cancers and inflammatory disorders.
- The specific role of NF-kappaB in intraprostatic inflammation remains largely uncharacterized.
- NF-kappaB activation influences the transcription of numerous genes involved in these processes.
Purpose of the Study:
- To investigate the role of NF-kappaB in intraprostatic inflammation using a novel molecular imaging approach.
- To assess the feasibility of using NF-kappaB-Luciferase Tag mice for noninvasive imaging of NF-kappaB activation.
- To evaluate the impact of pro-inflammatory cytokines on NF-kappaB activity in vivo.
Main Methods:
- Utilized transgenic NF-kappaB-Luciferase Tag mice for in vivo and ex vivo molecular imaging of NF-kappaB activation.
- Administered pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1 beta) systemically to induce NF-kappaB-dependent luminescence.
- Employed dexamethasone as an NF-kappaB inhibitor to modulate cytokine-induced luminescence.
Main Results:
- Cytokine administration induced time- and organ-specific increases in NF-kappaB-dependent luminescence.
- IL-1 beta administration led to the highest luminescence levels approximately 3-4 hours post-treatment.
- Chronic IL-1 beta administration demonstrated a cumulative effect on NF-kappaB activation within the prostate.
Conclusions:
- Molecular imaging of NF-kappaB activity offers a promising method to differentiate the roles of cytokine-induced NF-kappaB signaling in intraprostatic inflammation and prostate cancer.
- NF-kappaB-Luc mice serve as a valuable tool for screening potential therapeutic agents targeting inflammation and tumors associated with aberrant NF-kappaB activity.
- Dexamethasone's ability to reduce IL-1 beta-induced luminescence validates the utility of this model for drug discovery.
