Cell-Permeable Peptide Blocks TLR4 Signaling and Improves Islet Allograft Survival

Cell Transplantation
Huansheng DongHongjun Wang

Abstract

Toll-like receptor 4 (TLR4) activation in pancreatic β cells activates aberrant islet graft cellular pathways and contributes to immune rejection in allogeneic islet transplantation. As an approach to overcoming this problem, we determined the capacity of a 33-amino acid peptide consisting of a protein transduction domain (PTD) from the Hph-1 virus and a fragment of the intracellular domain of TLR4 from the C3H mice (PTD-dnTLR4) to block TLR4 signaling and improve allogeneic islet survival in vitro and after transplantation. The efficacy of PTD-dnTLR4 in blocking TLR4 signaling was assessed in the Raw264.7 macrophage line, in the islets, and the βTC3 cell line. In Raw264.7 cells, preculture with the peptide reduced LPS-induced NF-κB activation and production of proinflammatory cytokines (IL-1β, TNF-α, iNOS, and IL-6). In islets and β cells, preincubation with PTD-dnTLR4 suppressed LPS-induced TNF-α expression via inhibition of NF-κB activation and protected them from stress-induced cell death. In vivo, preincubation of BALB/c (H-2(d)) islets with PTD-dnTLR4 resulted in significantly longer survival than control islets in a streptozotocin-induced diabetes model (two of seven grafts survived long term >100 days). PTD-dnTLR4-treat...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·P Matzinger
Jan 21, 2001·The Journal of Biological Chemistry·Y OkamuraJ F Strauss
Apr 17, 2003·The Journal of Surgical Research·Marshall S BakerDixon B Kaufman
Jun 5, 2003·Current Molecular Medicine·Tsuneyasu Kaisho, Shizuo Akira
Aug 14, 2003·Biochemical and Biophysical Research Communications·Ulrika JohanssonOlle Korsgren
Jan 6, 2004·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·H E HohmeierC B Newgard
Aug 4, 2004·Cell Biochemistry and Biophysics·Arne AnderssonLeif Jansson
Aug 12, 2004·The Journal of Biological Chemistry·Stefan KrautwaldUlrich Kunzendorf
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Mar 26, 2005·Immunological Reviews·Ian R RifkinAnn Marshak-Rothstein
Jul 19, 2005·The Journal of Clinical Investigation·Liliana SchaeferHermann-Josef Gröne
Sep 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michal Cohen-SfadyIrun R Cohen
Feb 6, 2007·Seminars in Immunology·Taro Kawai, Shizuo Akira
May 4, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alyssa GoldbergHongjun Wang
May 15, 2007·Journal of Leukocyte Biology·Amy H TangJeffrey L Platt
Jul 28, 2007·The Journal of Clinical Investigation·Chrystal M PaulosNicholas P Restifo
Mar 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Seija LehnardtJoerg R Weber
Oct 3, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P FiorinaA Secchi
Feb 4, 2010·The Journal of Clinical Investigation·Nobuhide MatsuokaYohichi Yasunami
Jul 21, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Q GaoD P Yin
Sep 3, 2010·European Journal of Immunology·Bernd KrügerBernd Schröppel
Aug 5, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clara Westwell-RoperC Bruce Verchere
Apr 4, 2012·Cell Transplantation·Hongjun WangLeo E Otterbein
Oct 12, 2012·Cell Transplantation·Han RoJaeseok Yang

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Citations

Jan 22, 2017·Transplant International : Official Journal of the European Society for Organ Transplantation·Vaihere DelauneChristian Toso
Jun 17, 2020·Cell Transplantation·Cheng ChenWei Wang

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Methods Mentioned

BETA
PCR
Assay
flow cytometry
light microscopy

Software Mentioned

StatView
ImageJ

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