title: Notch Signaling Pathway Was Involved in Regulating Programmed Cell Death 1 Expression during Sepsis-Induced Immunosuppression.
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.
authors.affiliation: Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Tianyun
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin Er Road, Shanghai 200025, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Qu
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D060890:B7-H1 Antigen; D051880:Receptors, Notch