Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance

Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance

Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemic...

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Autores principales: Hu F, Wang H, Zhang S, Peng Y, Su L, Chang J, Liu G
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/41a12d028ba84c56978849e7d55615ed
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spelling oai:doaj.org-article:41a12d028ba84c56978849e7d55615ed2021-12-02T02:01:31ZInhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance1178-2013https://doaj.org/article/41a12d028ba84c56978849e7d55615ed2015-07-01T00:00:00Zhttp://www.dovepress.com/inhibition-of-myeloid-differentiation-factor-88-signaling-mediated-by--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88), which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester)(HGPAE) nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88). We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA), gene delivery, PAEHu FWang HZhang SPeng YSu LChang JLiu GDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4367-4382 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Hu F
Wang H
Zhang S
Peng Y
Su L
Chang J
Liu G
Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
description Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88), which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester)(HGPAE) nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88). We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA), gene delivery, PAE
format article
author Hu F
Wang H
Zhang S
Peng Y
Su L
Chang J
Liu G
author_facet Hu F
Wang H
Zhang S
Peng Y
Su L
Chang J
Liu G
author_sort Hu F
title Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
title_short Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
title_full Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
title_fullStr Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
title_full_unstemmed Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
title_sort inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/41a12d028ba84c56978849e7d55615ed
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AT wangh inhibitionofmyeloiddifferentiationfactor88signalingmediatedbyhistidinegraftedpolybetaaminoesteresternanovectorinducesdonorspecificliverallografttolerance
AT zhangs inhibitionofmyeloiddifferentiationfactor88signalingmediatedbyhistidinegraftedpolybetaaminoesteresternanovectorinducesdonorspecificliverallografttolerance
AT pengy inhibitionofmyeloiddifferentiationfactor88signalingmediatedbyhistidinegraftedpolybetaaminoesteresternanovectorinducesdonorspecificliverallografttolerance
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