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Posted by Raeky1@netzero.com on 15:18:25 2004/02/29
Published online: 8 February 2004, doi:10.1038/nm994
March 2004 Volume 10 Number 3 pp 305 - 309
A new cell-permeable peptide allows successful allogeneic islet transplantation in mice
Hirofumi Noguchi1, 2, 3, Masayuki Matsushita1, Teru Okitsu2, 3, Akiyoshi Moriwaki1, Kazuhito Tomizawa1, Sunghyun Kang4, Sheng-Tian Li1, Naoya Kobayashi2, Shinichi Matsumoto3, Koich Tanaka3, Noriaki Tanaka2 & Hideki Matsui1, 5
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 system1, 2. 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.
1. Department of Physiology and Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.
2. Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.
3. Department of Transplantation and Immunology, Kyoto University Hospital, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
4. Department of Pathology, Harvard Medical School and the Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
5. Protein Therapy, Preventure Program, Office of Technology Transfer, Japan Science and Technology Corporation, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.
Correspondence should be addressed to M Matsushita. e-mail: masayuki@cc.okayama-u.ac.jp
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