Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression

Programmed cell death 1 (PD-1) plays an important pathologic role in sepsis-induced immunosuppression. However, whether PD-1 overexpression occurs early during septic shock is unknown and its regulation mechanism is also unknown. Our study investigated the expressions of PD-1/programmed death-ligand...

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Main Authors: Tingting Pan, Zhaojun Liu, Jianyong Yin, Tianyun Zhou, Jialin Liu, Hongping Qu
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/539841
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author Tingting Pan
Zhaojun Liu
Jianyong Yin
Tianyun Zhou
Jialin Liu
Hongping Qu
author_facet Tingting Pan
Zhaojun Liu
Jianyong Yin
Tianyun Zhou
Jialin Liu
Hongping Qu
author_sort Tingting Pan
collection DOAJ
description Programmed cell death 1 (PD-1) plays an important pathologic role in sepsis-induced immunosuppression. However, whether PD-1 overexpression occurs early during septic shock is unknown and its regulation mechanism is also unknown. Our study investigated the expressions of PD-1/programmed death-ligand 1 (PD-L1) on immune cells in peripheral blood from the early-stage septic shock patients. We found that both PD-1 and PD-L1 showed increased expressions on the CD4+ T cells and monocytes. It indicated that PD-1 expression might be an early biomarker to assess illness severity and predict the prognosis of septic shock. Then, we further investigated the mechanism underlying the regulation of PD-1 expression. Our data showed that Notch signaling pathway was activated in both septic shock patients and lipopolysaccharide- (LPS-) tolerant THP1 cells and both interleukin-10 (IL-10) and PD-1 were increased in the THP1 cells. Inhibition of Notch signaling by N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenyl glycinet-butyl ester (DAPT) induced significantly decreased expressions of PD-1 and IL-10 in the LPS-tolerant cell model. Our work suggested that Notch signaling pathway was involved in the regulation of PD-1 expression.
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language English
publishDate 2015-01-01
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series Mediators of Inflammation
spelling doaj-art-c8b3c59d86bc40cbb21f156f52abf5a22025-08-20T02:19:41ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/539841539841Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced ImmunosuppressionTingting Pan0Zhaojun Liu1Jianyong Yin2Tianyun Zhou3Jialin Liu4Hongping Qu5Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaDepartment of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, ChinaProgrammed cell death 1 (PD-1) plays an important pathologic role in sepsis-induced immunosuppression. However, whether PD-1 overexpression occurs early during septic shock is unknown and its regulation mechanism is also unknown. Our study investigated the expressions of PD-1/programmed death-ligand 1 (PD-L1) on immune cells in peripheral blood from the early-stage septic shock patients. We found that both PD-1 and PD-L1 showed increased expressions on the CD4+ T cells and monocytes. It indicated that PD-1 expression might be an early biomarker to assess illness severity and predict the prognosis of septic shock. Then, we further investigated the mechanism underlying the regulation of PD-1 expression. Our data showed that Notch signaling pathway was activated in both septic shock patients and lipopolysaccharide- (LPS-) tolerant THP1 cells and both interleukin-10 (IL-10) and PD-1 were increased in the THP1 cells. Inhibition of Notch signaling by N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenyl glycinet-butyl ester (DAPT) induced significantly decreased expressions of PD-1 and IL-10 in the LPS-tolerant cell model. Our work suggested that Notch signaling pathway was involved in the regulation of PD-1 expression.http://dx.doi.org/10.1155/2015/539841
spellingShingle Tingting Pan
Zhaojun Liu
Jianyong Yin
Tianyun Zhou
Jialin Liu
Hongping Qu
Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
Mediators of Inflammation
title Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
title_full Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
title_fullStr Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
title_full_unstemmed Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
title_short Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression
title_sort notch signaling pathway was involved in regulating programmed cell death 1 expression during sepsis induced immunosuppression
url http://dx.doi.org/10.1155/2015/539841
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