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 IAd 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.
Written by:
Izgi K, Altuntas CZ, Bicer F, Ozer A, Sakalar C, Li X, Tuohy VK, Daneshgari F. Are you the author?
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.
Reference: PLoS One. 2013 Aug 16;8(8):e72067.
doi: 10.1371/journal.pone.0072067
PubMed Abstract
PMID: 23977210
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