title: Molecular imaging of nuclear factor-κB in bladder as a primary regulator of inflammatory response.
abstract: OBJECTIVE
  Nuclear factor-κB activation is implicated in chronic inflammatory disorders and it is a key regulator of genes involved in the response to infection, inflammation and stress. Interstitial cystitis and painful bladder syndrome are common inflammatory disorders of the bladder characterized by frequent urination and bladder pain. The role of nuclear factor-κB activation in bladder inflammation is not well defined.
  
  
  METHODS
  Female transgenic nuclear factor-κB-luciferase Tag mice (The Jackson Laboratory, Bar Harbor, Maine) were used to perform serial, noninvasive in vivo and ex vivo molecular imaging of nuclear factor-κB activation in the whole body after administering arsenic trioxide (5 mg/kg), lipopolysaccharide (2 mg/kg) or cyclophosphamide (Sigma®) (200 mg/kg) to initiate acute transient bladder inflammation. Pretreatment with dexamethasone (Sigma) (10 mg/kg) was used to modulate cyclophosphamide induced nuclear factor-κB dependent luminescence in vivo.
  
  
  RESULTS
  Treatment of nuclear factor-κB-luciferase Tag mice with chemicals increased luminescence in a time and organ specific manner in vivo and ex vivo. The highest levels of bladder nuclear factor-κB dependent luminescence were observed 4 hours after cyclophosphamide administration. Pretreatment with dexamethasone 1 hour before cyclophosphamide injection significantly down-regulated cyclophosphamide induced bladder nuclear factor-κB dependent luminescence, ameliorated the grossly evident pathological features of acute inflammation and decreased cellular immunostaining for nuclear factor-κB in the bladder.
  
  
  CONCLUSIONS
  Nuclear factor-κB activity may have an important role in the pathophysiology of bladder inflammation. Nuclear factor-κB-luciferase mice can serve as a useful model in which to screen potential candidate drugs for cystitis associated with aberrant nuclear factor-κB activity. Such screening may significantly aid the development of therapeutic strategies to manage inflammatory bladder disorders.
authors.affiliation: Case Western Reserve University and The Urology Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Vykhovanets
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.forename: Olena V
authors.initials: OV
authors.lastname: Vykhovanets
authors.forename: Edward E
authors.initials: EE
authors.lastname: Cherullo
authors.forename: Lee E
authors.initials: LE
authors.lastname: Ponsky
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D003556:Cystitis / Q000209:etiology*; D005260:Female; D051379:Mice; D057054:Molecular Imaging; D016328:NF-kappa B / Q000502:physiology*
chemical_list: D016328:NF-kappa B
references.citation: J Urol. 1999 Nov;162(5):1812-6
references.pmid: 10524940
references.citation: Am J Pathol. 2008 Jan;172(1):59-67
references.pmid: 18079438
references.citation: J Urol. 2007 Jun;177(6):2042-9
references.pmid: 17509284
references.citation: Curr Urol Rep. 2008 Jul;9(4):314-9
references.pmid: 18765131
references.citation: Biochem Pharmacol. 2000 Oct 15;60(8):1041-9
references.pmid: 11007940
references.citation: Toxicol Sci. 2008 Dec;106(2):350-63
references.pmid: 18728046
references.citation: J Urol. 2002 May;167(5):2229-34
references.pmid: 11956484
references.citation: Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001651
references.pmid: 20457564
references.citation: Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov;3(7):583-90
references.pmid: 7827589
references.citation: J Urol. 2009 May;181(5):2339-48
references.pmid: 19303104
references.citation: Oncogene. 2006 Oct 30;25(51):6831-43
references.pmid: 17072331
references.citation: Prostate. 2009 May 1;69(6):633-43
references.pmid: 19170127
references.citation: Clin Diagn Lab Immunol. 2004 Sep;11(5):969-76
references.pmid: 15358661
references.citation: J Urol. 1998 Dec;160(6 Pt 1):2000-3
references.pmid: 9817309
references.citation: Mol Cell Biol. 1999 Jul;19(7):4798-805
references.pmid: 10373529
references.citation: Am J Med. 2002 Jul 8;113 Suppl 1A:14S-19S
references.pmid: 12113867
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R677-85
references.pmid: 17537839
references.citation: J Urol. 2000 Mar;163(3):993-8
references.pmid: 10688037
references.citation: Toxicol Appl Pharmacol. 2010 Apr 15;244(2):99-105
references.pmid: 20045014
references.citation: Prostate. 2008 Jan 1;68(1):34-41
references.pmid: 18004768