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Molecular Imaging of Nuclear Factor-κB in Bladder as a Primary Regulator of Inflammatory Response

2011; Lippincott Williams & Wilkins; Volume: 187; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2011.09.007

1527-3792

Eugene V. Vykhovanets, Gregory T. MacLennan, Olena Vykhovanets, Edward E. Cherullo, Lee Ponsky, Sanjay Gupta,

Dermatology and Skin Diseases

No AccessJournal of UrologyInvestigative Urology1 Jan 2012Molecular Imaging of Nuclear Factor-κB in Bladder as a Primary Regulator of Inflammatory Response Eugene V. Vykhovanets, Gregory T. MacLennan, Olena V. Vykhovanets, Edward E. Cherullo, Lee E. Ponsky, and Sanjay Gupta Eugene V. VykhovanetsEugene V. Vykhovanets More articles by this author , Gregory T. MacLennanGregory T. MacLennan More articles by this author , Olena V. VykhovanetsOlena V. Vykhovanets More articles by this author , Edward E. CherulloEdward E. Cherullo More articles by this author , Lee E. PonskyLee E. Ponsky Financial interest and/or other relationship with Accurax, Tengion, US Endoscopy and Varia Medical System. More articles by this author , and Sanjay GuptaSanjay Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.09.007AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and 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. References 1 : Interstitial cystitis and painful bladder syndrome. J Urol2007; 177: 2042. Link, Google Scholar 2 : Anxiety in functional pain disorders. In: Functional Pain Syndromes: Presentation and Pathophysiology. Edited by . 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Link, Google Scholar Departments of Urology and Pathology (GTM), Case Western Reserve University and The Urology Institute, University Hospitals Case Medical Center, Cleveland, Ohio© 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 1January 2012Page: 330-337 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.KeywordsNF-kappa Bmolecular imagingluminescenceurinary bladderinflammationMetricsAuthor Information Eugene V. Vykhovanets More articles by this author Gregory T. MacLennan More articles by this author Olena V. Vykhovanets More articles by this author Edward E. Cherullo More articles by this author Lee E. Ponsky Financial interest and/or other relationship with Accurax, Tengion, US Endoscopy and Varia Medical System. More articles by this author Sanjay Gupta More articles by this author Expand All Advertisement PDF downloadLoading ...