MP72-05 TOLL-LIKE RECEPTOR ACTIVATION IS ASSOCIATED WITH BLADDER INFLAMMATION, PELVIC PAIN AND VOIDING DYSFUNCTION IN A TRANSGENIC INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME-LIKE ANIMAL MODEL: A MAPP RESEARCH NETWORK ANIMAL MODEL STUDY

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2016MP72-05 TOLL-LIKE RECEPTOR ACTIVATION IS ASSOCIATED WITH BLADDER INFLAMMATION, PELVIC PAIN AND VOIDING DYSFUNCTION IN A TRANSGENIC INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME-LIKE ANIMAL MODEL: A MAPP RESEARCH NETWORK ANIMAL MODEL STUDY Yaoqin Wang, Suming Xu, Michael O'Donnell, Susan Lutgendorf, Pengchao Li, Lang Feng, Catherine Bradley, Bradley Erickson, Vincent Magnotta, Karl Kreder, and Yi Luo Yaoqin WangYaoqin Wang More articles by this author , Suming XuSuming Xu More articles by this author , Michael O'DonnellMichael O'Donnell More articles by this author , Susan LutgendorfSusan Lutgendorf More articles by this author , Pengchao LiPengchao Li More articles by this author , Lang FengLang Feng More articles by this author , Catherine BradleyCatherine Bradley More articles by this author , Bradley EricksonBradley Erickson More articles by this author , Vincent MagnottaVincent Magnotta More articles by this author , Karl KrederKarl Kreder More articles by this author , and Yi LuoYi Luo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1618AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Toll-like receptor (TLR) activation has been demonstrated in several chronic pain conditions but has not been well explored in IC/BPS. We previously showed that peripheral blood mononuclear cells from IC/BPS patients produced elevated proinflammatory cytokines in response to TLR2/4 stimulations, indicating the presence of altered peripheral TLR activation in IC/BPS. Here we used our validated transgenic autoimmune cystitis model (URO-OVA) that reproduces many clinical features of IC/BPS to further investigate whether central and peripheral TLR activations are associated with bladder inflammation, pelvic pain and voiding dysfunction seen in human IC/BPS. METHODS URO-OVA mice (n=8) were induced for cystitis by adoptive transfer of antigen specific CD8+ T cells. At day 7 after cystitis induction mice were analyzed for pelvic pain (von Frey filament stimulation), voiding dysfunction (micturition cages) and bladder inflammation (H&E staining). Splenocytes were prepared and stimulated with escalating doses of Pam3CSK4 (a TLR2 agonist) or lipopolysaccharide (LPS, a TLR4 agonist) ranging 10-5-102 µg/ml for 24 hrs, followed by ELISA analysis of proinflammatory cytokines in the conditioned culture supernatants. Lumbar spinal cords were processed for total RNA extraction and RT-PCR analysis of mRNAs for proinflammatory cytokines, TLR and glial activation markers. URO-OVA mice (n=8) not induced for cystitis were analyzed in parallel. RESULTS After cystitis induction URO-OVA mice developed profound bladder histopathology, increased pelvic responses to von Frey filament stimulation (p<0.05 for all applied forces ranging 0.04-4 g), increased urinary frequency (control 4.86±0.634 vs. cystitis 9.0±0.447 voids, p<0.001), and decreased average volume voided per micturition (control 0.26±0.036 vs. cystitis 0.14±0.016 g, p=0.022). These changes were associated with increased splenocyte production of IL-1ß, IL-6 and TNF-a in response to TLR2/4 stimulations. Elevated expressions of IL-6, TNF-a, TLR4 and CD11b mRNAs in the lumbar spinal cords were observed in cystitis-induced mice, which was also associated with phenotypic and functional changes. CONCLUSIONS Central and peripheral TLR activations are associated with bladder inflammation, pelvic pain and voiding dysfunction in URO-OVA mice, providing a potential mechanistic insight for human IC/BPS. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e953-e954 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yaoqin Wang More articles by this author Suming Xu More articles by this author Michael O'Donnell More articles by this author Susan Lutgendorf More articles by this author Pengchao Li More articles by this author Lang Feng More articles by this author Catherine Bradley More articles by this author Bradley Erickson More articles by this author Vincent Magnotta More articles by this author Karl Kreder More articles by this author Yi Luo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...