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Molecular imaging of NF‐kappaB in prostate tissue after systemic administration of IL‐1β
Author(s) -
Vykhovanets Eugene V.,
Shukla Sanjeev,
MacLennan Gregory T.,
Resnick Martin I.,
Carlsen Harald,
Blomhoff Rune,
Gupta Sanjay
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20666
Subject(s) - nf κb , inflammation , prostate cancer , cytokine , systemic administration , luciferase , in vivo , medicine , cancer research , prostate , ex vivo , dexamethasone , interleukin 6 , nfkb1 , transcription factor , biology , cancer , transfection , gene , biochemistry , microbiology and biotechnology
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. Prostate 68: 34–41, 2008. © 2007 Wiley‐Liss, Inc.