RDP58 inhibits T cell-mediated bladder inflammation in an autoimmune cystitis model.
Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder with a strong autoimmune component. Currently, the major challenge in IC treatment is the development of effective therapies. RDP58 is a novel d-amino acid decapeptide with potent immunosuppressive activity. In this study, we investigated whether RDP58 was effective as an intravesical agent for treating bladder autoimmune inflammation in a transgenic mouse model (URO-OVA mice). URO-OVA mice were adoptively transferred with syngeneic activated splenocytes of OT-I mice transgenic for the OVA-specific CD8(+) TCR for cystitis induction and treated intravesically with RDP58 at days 0 and 3. Compared with controls, the RDP58-treated bladders showed markedly reduced histopathology and expressions of mRNAs and proteins of TNF-alpha, NGF and substance P. To determine whether the inhibition of bladder inflammation by RDP58 was due to the interference with effector T cells, we treated the cells with RDP58 in vitro. Cells treated with RDP58 showed reduced production of TNF-alpha and IFN-gamma as well as apoptotic death. Collectively, these results indicate that RDP58 is effective for treating T cell-mediated experimental autoimmune cystitis and may serve as a useful intravesical agent for the treatment of autoimmune-associated bladder inflammation such as IC.
Liu
Wujiang
W
Department of Urology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 3202 MERF, 375 Newton Road, IA 52242-1087, USA.
Deyoung
Barry R
BR
Chen
Xiaohong
X
Evanoff
David P
DP
Luo
Yi
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003556:Cystitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015552:Injections, Intralesional; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; C092373:allotrap