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Mediators of Inflammation
Volume 2015, Article ID 539841, 9 pages
http://dx.doi.org/10.1155/2015/539841
Research Article

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

1Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China
2Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China

Received 10 February 2015; Revised 13 April 2015; Accepted 14 April 2015

Academic Editor: Stefanie B. Flohé

Copyright © 2015 Tingting Pan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.