Prolongation of skin graft survival by exogenous ubiquitin

Steven A. Earle, Ahmed El-Haddad, Mayur B. Patel, Phillip Ruiz, Si M. Pham, Matthias Majetschak

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Recently, it was shown that exogenous ubiquitin has anti-inflammatory actions in vivo and that the ubiquitin-decapeptide 50-59 has immunosuppressive effects similar to cyclosporine. Immunosuppressive effects of the native ubiquitin molecule and its therapeutic potential in transplantation are unknown. We tested the hypothesis that ubiquitin inhibits alloreactivity and increases allograft survival in a murine model of skin transplantation in fully mismatched strain combinations (C3H/HEJ-DBA2). Ubiquitin dose-dependently inhibited mixed leukocyte reaction in C3H/HEJ splenocytes in vitro. Intraperitoneal ubiquitin administration (25 μg/h for 14 days) was well-tolerated, dose-dependently increased ubiquitin serum concentrations and median allograft survival from 10 days (with albumin; control) to 17 days in DBA2 mice (survival ratio: 1.7, 95% confidence interval: 1.266-2.134; P=0.0005). The in vivo effects in this study combined with our previous work strongly indicate that ubiquitin is a potent immune modulator with broad therapeutic potential. Ubiquitin treatment could be a novel strategy to improve immunosuppressive regimens in transplantation.

Original languageEnglish (US)
Pages (from-to)1544-1546
Number of pages3
JournalTransplantation
Volume82
Issue number11
DOIs
StatePublished - Dec 1 2006

Keywords

  • Immune modulation
  • Immunophilin
  • Therapeutic potential
  • Transplantation
  • Ubiquitin

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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