Uroplakin Peptide-Specific Autoimmunity Initiates Interstitial Cystitis/Painful Bladder Syndrome in Mice

被引:31
作者
Izgi, Kenan [1 ,2 ]
Altuntas, Cengiz Z. [1 ]
Bicer, Fuat [1 ,2 ]
Ozer, Ahmet [1 ,3 ]
Sakalar, Cagri [4 ]
Li, Xiaoxia [4 ]
Tuohy, Vincent K. [4 ]
Daneshgari, Firouz [1 ]
机构
[1] Case Western Reserve Univ, Dept Urol, Cleveland, OH 44106 USA
[2] Cleveland State Univ, Dept Clin Chem, Cleveland, OH 44115 USA
[3] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA
[4] Cleveland Clin, Dept Immunol, Lerner Res Inst, Cleveland, OH 44106 USA
来源
PLOS ONE | 2013年 / 8卷 / 08期
关键词
LOWER URINARY-TRACT; POTENTIAL ANIMAL-MODEL; VISCERAL PAIN; SYNDROME/INTERSTITIAL CYSTITIS; CYCLOPHOSPHAMIDE CYSTITIS; NEUROGENIC CYSTITIS; INTERFERON-GAMMA; MURINE MODEL; INFLAMMATION; RAT;
D O I
10.1371/journal.pone.0072067
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) is enigmatic. Autoimmunity and impaired urothelium might lead the underlying pathology. A major shortcoming in IC/PBS research has been the lack of an appropriate animal model. In this study, we show that the bladder specific uroplakin 3A-derived immunogenic peptide UPK3A 65-84, which contains the binding motif for IA(d) MHC class II molecules expressed in BALB/c mice, is capable of inducing experimental autoimmune cystitis in female mice of that strain. A highly antigen-specific recall proliferative response of lymph node cells to UPK3A 65-84 was observed, characterized by selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype, including enhanced production of interferon gamma and interleukin-2. T cell infiltration of the bladder and bladder-specific increased gene expression of inflammatory cytokines were observed. Either active immunization with UPK3A 65-84 or adoptive transfer of peptide-activated CD4+ T cells induced all of the predominant IC/PBS phenotypic characteristics, including increased micturition frequency, decreased urine output per micturition, and increased pelvic pain responses to stimulation with von Frey filaments. Our study demonstrates the creation of a more specific experimental autoimmune cystitis model that is the first inducible model for IC/PBS that manifests all of the major symptoms of this debilitating condition.
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页数:10
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