A new cell-permeable peptide allows successful allogeneic islet transplantation in mice

• Published in: Nature medicine Vol. 10; no. 3; pp. 305 - 309
• Main Authors: Matsushita, Masayuki, Noguchi, Hirofumi, Okitsu, Teru, Moriwaki, Akiyoshi, Tomizawa, Kazuhito, Kang, Sunghyun, Li, Sheng-Tian, Kobayashi, Naoya, Matsumoto, Shinichi, Tanaka, Koich, Tanaka, Noriaki, Matsui, Hideki
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2004
• Subjects: Animals; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Graft Survival; Humans; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - pharmacology; Insulin - metabolism; Insulin Secretion; Interleukin-2 - metabolism; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans Transplantation; Jurkat Cells; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; NFATC Transcription Factors; Nuclear Proteins; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - metabolism; Peptides; Permeability; Recombinant Fusion Proteins - pharmacology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tacrolimus - metabolism; Tacrolimus - pharmacology; Transcription Factors - antagonists & inhibitors; Transcription Factors - metabolism; Transplantation, Homologous
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm994

Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.