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Notch signaling suppresses CD14 + monocytes cells activity in patients with chronic hepatitis C
Author(s) -
Zhang ZhiHong,
Wang Han,
Zhang DongNa,
Zhu GuangZe
Publication year - 2019
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12980
Subject(s) - cd14 , monocyte , immunology , notch signaling pathway , interferon , cytokine , biology , virology , medicine , signal transduction , immune system , microbiology and biotechnology
Hepatitis C virus (HCV) infection always leads to chronic hepatitis via dysregulation of host immunity. Notch signaling also modulates the response of monocytes/macrophages. Thus, we aimed to investigate the regulatory role of Notch signaling to CD14 + monocytes. Forty patients with chronic hepatitis C and twenty normal controls (NC) were enrolled. CD14 + monocytes and CD4 + T cells were purified from peripheral bloods. Notch receptors' mRNA expression in CD14 + monocytes was semi‐quantified by real‐time PCR. Cytokine production by CD14 + monocytes in response to γ‐secretase inhibitor (GSI) was investigated by ELISA. GSI‐induced CD14 + monocytes activity to HCV clearance in Huh7.5 cells and to CD4 + T cell differentiation was also assessed in direct and indirect contact co‐culture system. Notch1 mRNA relative level was approximately 10‐fold elevated in CD14 + monocytes from chronic hepatitis C patients when compared with NC. GSI stimulation resulted in enhanced cytokines production by CD14 + monocytes from chronic hepatitis C patients. GSI‐stimulated CD14 + monocytes from chronic hepatitis C patients induced suppression of HCV RNA replication in both direct and indirect contact co‐culture system of CD14 + monocytes and HCVcc‐infected Huh7.5 cells, and this process was accompanied by elevation of interferon‐γ production but not increased target cell death. Moreover, GSI stimulation also enhanced CD14 + monocytes‐induced Th1 and Th17 cells activation, and this process required direct cell‐to‐cell contact. Effective antiviral therapy down‐regulated Notch1 mRNA expression and promoted cytokine production by CD14 + monocytes from chronic hepatitis C. Current data revealed an important immunoregulatory property of Notch signaling to CD14 + monocytes in chronic HCV infection.