A new cell-permeable peptide allows successful allogeneic islet transplantation in mice.
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.
Noguchi
Hirofumi
H
Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.
Matsushita
Masayuki
M
Okitsu
Teru
T
Moriwaki
Akiyoshi
A
Tomizawa
Kazuhito
K
Kang
Sunghyun
S
Li
Sheng-Tian
ST
Kobayashi
Naoya
N
Matsumoto
Shinichi
S
Tanaka
Koich
K
Tanaka
Noriaki
N
Matsui
Hideki
H
D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007376:Interleukin-2 / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides; D010539:Permeability; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014184:Transplantation, Homologous
D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007328:Insulin; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009842:Oligopeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C121611:VIVIT peptide; C015462:polyarginine; D016559:Tacrolimus