title: Molecular imaging of NF-kappaB in prostate tissue after systemic administration of IL-1 beta.
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.
authors.affiliation: Department of Urology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Vykhovanets
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Shukla
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.forename: Martin I
authors.initials: MI
authors.lastname: Resnick
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics*; D011467:Prostate / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D008156:Luciferases