title: Uroplakin peptide-specific autoimmunity initiates interstitial cystitis/painful bladder syndrome in mice.
abstract: 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 γ 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.
authors: Department of Urology, Case Western Reserve University, Cleveland, Ohio, United States of America ; Department of Clinical Chemistry, Cleveland State University, Cleveland,, Ohio, United States of America.
authors: Kenan
authors: K
authors: Izgi
authors: Cengiz Z
authors: CZ
authors: Altuntas
authors: Fuat
authors: F
authors: Bicer
authors: Ahmet
authors: A
authors: Ozer
authors: Cagri
authors: C
authors: Sakalar
authors: Xiaoxia
authors: X
authors: Li
authors: Vincent K
authors: VK
authors: Tuohy
authors: Firouz
authors: F
authors: Daneshgari
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D002478:Cells, Cultured; D003556:Cystitis; D018856:Cystitis, Interstitial / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D001743:Urinary Bladder / Q000276:immunology / Q000503:physiopathology; D014554:Urination; D060171:Uroplakin III / Q000737:chemistry / Q000276:immunology*
chemical_list: D010446:Peptide Fragments; C554661:Upk3a protein, mouse; D060171:Uroplakin III
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