Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2017MP26-09 INVOLVEMENT OF TOLL-LIKE RECEPTOR 4 IN NONBACTERIAL BLADDER INFLAMMATION AND FREQUENT URINATION VIA INFLAMMASOME PATHWAYS IN SPONTANEOUSLY HYPERTENSIVE RATS Shinsuke Mizoguchi, Kenichi Mori, Naoyuki Yamanaka, Fuminori Sato, Naoki Yoshimura, and Hiromitsu Mimata Shinsuke MizoguchiShinsuke Mizoguchi More articles by this author , Kenichi MoriKenichi Mori More articles by this author , Naoyuki YamanakaNaoyuki Yamanaka More articles by this author , Fuminori SatoFuminori Sato More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Hiromitsu MimataHiromitsu Mimata More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.780AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although several studies have suggested that chronic bladder inflammation associated with oxidative stress contribute to overactive bladder (OAB), the underlying pathophysiological mechanism is unclear. Recently, the toll-like receptor (TLR) 4 has been reported to play a role in triggering chronic inflammatory conditions through activation of NLRP3 inflammasome pathways followed by production of IL1β and IL18. Although oxidative stress is one of factors that activate TLR4, it is not known whether changes in the expression of TLR4 are involved in the development of OAB caused by chronic inflammation. We therefore investigated an alteration of histopathology and expression of TLR4 and NLRP3 inflammasome-related molecules in the bladder using spontaneously hypertensive rats (SHRs) as an OAB model. METHODS Twenty-weeks-old male SHRs and Wistar Kyoto rats (control) were used. After voiding function was analyzed by using metabolic cages, the bladder was excised for analysis of histopathology and mRNA expression. Hematoxylin eosin and Masson′s trichrome stain were performed to analyze bladder inflammatory condition and fibrosis. Immunohistostaining for NLRP3, TLR4 was also performed. Expression levels of NLRP3, IL1β, IL-18, IL6, IL8 and TGFβ mRNA in the bladder were investigated by real-time PCR. Statistical analysis was performed using Mann-Whitney U test. P value less than 0.05 was considered statistically significant. RESULTS In voiding function analyses, single urine volume was significantly decreased and voiding frequency was significantly increased in SHRs compared to control rats. In histological evaluation, suburothelial fibrosis was shown in SHRs compared to controls. Furthermore, immunohistostaining showed localized expression of NLRP3 and TLR4 in the bladder urothelium in both groups. In RT-qPCR analyses, mRNA expression levels of NLRP3, TLR4, IL1β, IL-18, IL6, IL8 and TGFβ were significantly increased in SHRs in the bladder compared to controls. CONCLUSIONS These results suggest that activation of TLR4 associated with oxidative stress is implicated in bladder chronic inflammation, which leads to frequent urination through NLRP3 inflammasome pathways. Therefore, further clarification of interactions between TLR4 and inflammasome pathways may offer new therapeutic targets for OAB associated with chronic inflammation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e322-e323 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Shinsuke Mizoguchi More articles by this author Kenichi Mori More articles by this author Naoyuki Yamanaka More articles by this author Fuminori Sato More articles by this author Naoki Yoshimura More articles by this author Hiromitsu Mimata More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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