Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice
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ORIGINAL ARTICLE
Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice Xing-Wei Jin,1 Bo-Ke Liu,1 Xiang Zhang,1 Zhong-Hua Zhao,2 and Yuan Shao1,3,4
Abstract—The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund’s adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund’s adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic–pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1β, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1β, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in doubleimmunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC. KEY WORDS: autoimmune cystitis model; interstitial cystitis; bladder pain syndrome; C57BL/6.
INTRODUCTION Xing-Wei Jin and Bo-Ke Liu contributed equally to this work. 1
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China 2 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China 3 Department of Urology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China 4 To whom correspondence should be addressed at Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China. E-mail: [email protected] Abbreviations: BPS, Bladder pain syndrome; CFA, Complete Freund’s adjuvant; EAC, Experimental autoimmune cystitis; IC, Interstitial cystitis; IFA, Incomplete Freund’s adjuvant; MHC, Major histocompatibility complex; NK1R, Neurokinin 1 receptor; SP, Substance P
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic, painful, and disabling disease ass
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