Carbamylated Erythropoietin Regulates Immune Responses and Promotes Long-Term Kidney Allograft Survival Through Activation of PI3K/AKT Signaling

2019 ◽  
Author(s):  
Ning Na ◽  
Daqiang Zhao ◽  
Jinhua Zhang ◽  
Shicong Yang ◽  
Dielai Xie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Akt Signaling ◽  
Allograft Survival ◽  
Kidney Allograft ◽  
Carbamylated Erythropoietin

scholarly journals Carbamylated erythropoietin regulates immune responses and promotes long-term kidney allograft survival through activation of PI3K/AKT signaling

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Ning Na ◽  
Daqiang Zhao ◽  
Jinhua Zhang ◽  
Jiaqing Wu ◽  
Bin Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Akt Signaling ◽  
Control Group ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Allograft Survival ◽  
Kidney Allograft

Abstract Modulation of alloimmune responses is critical to improving transplant outcome and promoting long-term graft survival. To determine mechanisms by which a nonhematopoietic erythropoietin (EPO) derivative, carbamylated EPO (CEPO), regulates innate and adaptive immune cells and affects renal allograft survival, we utilized a rat model of fully MHC-mismatched kidney transplantation. CEPO administration markedly extended the survival time of kidney allografts compared with the transplant alone control group. This therapeutic effect was inhibited when the recipients were given LY294002, a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway or anti-EPO receptor (EPOR) antibody, in addition to CEPO. In vitro, CEPO inhibited the differentiation and function of dendritic cells and modulated their production of pro-inflammatory and anti-inflammatory cytokines, along with activating the PI3K/AKT signaling pathway and increasing EPOR mRNA and protein expression by these innate immune cells. Moreover, after CD4+ T cells were exposed to CEPO the Th1/Th2 ratio decreased and the regulatory T cell (Treg)/Th17 ratio increased. These effects were abolished by LY294002 or anti-EPOR antibody, suggesting that CEPO regulates immune responses and promotes kidney allograft survival by activating the PI3K/AKT signaling pathway in an EPOR-dependent manner. The immunomodulatory and specific signaling pathway effects of CEPO identified in this study suggest a potential therapeutic approach to promoting kidney transplant survival.

scholarly journals SP801TOLL-LIKE RECEPTOR M-RNA EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH LONG-TERM KIDNEY ALLOGRAFT SURVIVAL

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii642-iii642
Author(s):  
Sławomir C. Zmonarski ◽  
Katarzyna Koscielska ◽  
Madziarska Katarzyna ◽  
Myszka Marta ◽  
Magott-Procelewska Maria ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rna Expression ◽  
Allograft Survival ◽  
Peripheral Blood Mononuclear ◽  
Kidney Allograft ◽  
Blood Mononuclear Cells

Donor Age Amplifies the Detrimental Effects of Cold Ischemia Time on Long-Term Kidney Allograft Survival Independently of the Occurrence of Delayed Graft Function or Early Acute Rejection

2020 ◽  
Vol 18 (4) ◽  
pp. 436-443
Author(s):  
Pedro Rincon Cintra da Cruz ◽  
Aderivaldo Cabral Dias Filho ◽  
Viviane Brandão Bandeira Mello Santana ◽  
Rubia Bethania Biela Boaretto ◽  
Cassio Luis Zanettini Riccetto
Keyword(s):  
Acute Rejection ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Cold Ischemia Time ◽  
Donor Age ◽  
Allograft Survival ◽  
Cold Ischemia ◽  
Kidney Allograft ◽  
Ischemia Time

scholarly journals LATE ACUTE REJECTION - AN IMPACT ON THE LONG-TERM KIDNEY ALLOGRAFT SURVIVAL

2010 ◽  
Vol 90 ◽  
pp. 865 ◽  
Author(s):  
A. Kukla ◽  
R. Leduc ◽  
D. Schladt ◽  
B. Najafian ◽  
B. Kasiske ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Allograft Survival ◽  
Kidney Allograft

INFLUENCE OF A POSITIVE HISTORICAL ANTIHUMAN GLOBULIN CROSSMATCH ON LONG TERM KIDNEY ALLOGRAFT SURVIVAL

1998 ◽  
Vol 65 (12) ◽  
pp. S68
Author(s):  
C. Baron ◽  
R. Bentabet ◽  
D. Dahmane ◽  
T. Seror ◽  
P. Bierling ◽  
...  
Keyword(s):  
Allograft Survival ◽  
Kidney Allograft

scholarly journals Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival

2016 ◽  
Vol 89 (5) ◽  
pp. 1119-1124 ◽  
Author(s):  
G.V. Ramesh Prasad ◽  
Sailesh Ananth ◽  
Sneha Palepu ◽  
Michael Huang ◽  
Michelle M. Nash ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplantation ◽  
Important Risk Factor ◽  
Allograft Survival ◽  
Kidney Allograft

scholarly journals Long-term patient survival and kidney allograft survival in post-transplant diabetes mellitus: a single-center retrospective study

2016 ◽  
Vol 29 (9) ◽  
pp. 1017-1028 ◽  
Author(s):  
Thomas Dienemann ◽  
Naohiko Fujii ◽  
Yimei Li ◽  
Shivali Govani ◽  
Nikitha Kosaraju ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Retrospective Study ◽  
Patient Survival ◽  
Single Center ◽  
Allograft Survival ◽  
Kidney Allograft ◽  
Post Transplant

Neutralising IL-12 Activity as a Strategy for Prolonging Allograft Survival and Preventing Graft-Versus-Host Disease

1998 ◽  
Vol 43 (4) ◽  
pp. 109-111 ◽  
Author(s):  
D.J. Orr ◽  
E.M. Bolton ◽  
J.A. Bradley
Keyword(s):  
Immune Responses ◽  
Graft Versus Host Disease ◽  
Interleukin 12 ◽  
Murine Models ◽  
Allograft Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Immunoregulatory Cytokine ◽  
Dependent Cell

Interleukin-12 (IL-12) is a key immunoregulatory cytokine which promotes the development of Thl-dependent, cell-mediated immune responses. Acute allograft rejection after organ transplantation and acute graft-versus-host disease (G VHD) after bone-marrow transplantation are generally attributed to cell-mediated immune mechanisms and, therefore, potentially susceptible to immunological intervention at the level of IL-12. Recent data from murine models of transplantation have highlighted the potential of IL-12 as a selective target for immunotherapy. Neutralising endogenous IL-12 for a brief period at the time of transplant promotes long-term deviation from a Thl to a polarised Th2 alloimmune response. This confers lasting protection from GVHD but is less effective at preventing acute rejection, possibly because Th2-dependent immune responses are also capable of effecting graft rejection.

81-P: Post-transplant anti-MICA antibodies and long-term kidney allograft survival

2009 ◽  
Vol 70 ◽  
pp. S52
Author(s):  
Patricia Grenzi ◽  
Erika F. Campos ◽  
Helio Tedesco-Silva ◽  
Marcello Franco ◽  
Jose O. Medina-Pestana ◽  
...  
Keyword(s):  
Allograft Survival ◽  
Kidney Allograft ◽  
Post Transplant
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