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RDP58 inhibits T cell-mediated bladder inflammation in an autoimmune cystitis model.

Abstract
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.
AuthorsWujiang Liu, Barry R Deyoung, Xiaohong Chen, David P Evanoff, Yi Luo
JournalJournal of autoimmunity (J Autoimmun) Vol. 30 Issue 4 Pg. 257-65 (Jun 2008) ISSN: 0896-8411 [Print] England
PMID18162370 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cytokines
  • Immunosuppressive Agents
  • Peptides
  • allotrap
Topics
  • Animals
  • Autoimmune Diseases (drug therapy, immunology, pathology)
  • CD8-Positive T-Lymphocytes (drug effects, immunology)
  • Cystitis (drug therapy, immunology, pathology)
  • Cytokines (biosynthesis, drug effects)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunosuppressive Agents (administration & dosage)
  • Injections, Intralesional
  • Mice
  • Mice, Transgenic
  • Peptides (administration & dosage)
  • Reverse Transcriptase Polymerase Chain Reaction

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