Interaction of notch signaling pathway with toll-like receptor 4 on the function of CD14+ monocytes in chronic hepatitis C patients
10.3760/cma.j.issn.1007-3418.2019.07.010
- VernacularTitle: Notch信号通路与Toll样受体4的相互作用对慢性丙型肝炎患者CD14+单核细胞功能的影响
- Author:
Yu LI
1
;
Lianxiang LI
2
;
Xianjiao ZHANG
3
;
Lijie YUAN
1
;
Fengyu XI
4
;
Hong ZHANG
1
;
Lixia ZHANG
4
Author Information
1. Department of Infectious Diseases, Shaanxi Provincial People’s Hospital and The Affiliated Hospital of Xi’an Medical University, Xi’an 710068, China
2. Department of Gynecology, Shaanxi Provincial Hospital People’s Hospital and The Affiliated Hospital of Xi’an Medical University, Xi’an 710068, China
3. Department of Scientific Research, Shaanxi Provincial People’s Hospital and The Affiliated Hospital of Xi’an Medical University, Xi’an 710068, China
4. Department of Clinical Laboratory, Shaanxi Provincial People’s Hospital and The Affiliated Hospital of Xi’an Medical University, Xi’an 710068, China
- Publication Type:Journal Article
- Keywords:
Hepatitis C, chronic;
Notch signaling;
Toll-like receptor 4;
CD14+ monocytes
- From:
Chinese Journal of Hepatology
2019;27(7):527-532
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the expressional changes in Notch signaling pathway and toll-like receptor 4 (TLR4) and their interactions on the functions of CD14+ monocytes in chronic hepatitis C patients.
Methods:A total of 24 treatment-naïve chronic hepatitis C cases and 10 healthy individuals, who visited Shaanxi Provincial People's Hospital from August to October 2017, were enrolled. Selected CD14+ monocytes were stimulated by the Notch signaling pathway inhibitor DAPT or transfected with TLR4 siRNA, and the levels of Notch1, Notch2, Hes1 and Hes5 mRNA were detected by real-time quantitative PCR. TLR4 protein levels and phosphorylation of NF-κB was detected by Western blot. ELISA was used to detect the level of cytokines secreted from CD14+ monocytes. A t-test or paired t-test was used for comparison between groups.
Results:The relative expression of Notch1 mRNA (3.97 ± 2.03 vs. 0.91 ± 0.76, P < 0.01) and downstream of Notch signaling pathway (5.96 ± 2.31 vs. 0.99 ± 0.45, P < 0.01), Hes1 mRNA and Hes5 mRNA (4.31 ± 1.05 vs. 0.84 ± 0.20, P < 0.01) in CD14+ monocytes of chronic hepatitis C patients was significantly higher than that of healthy individuals. The relative expression of TLR4 mRNA (5.14 ± 1.09 vs. 1.27 ± 0.39) and protein level in CD14+ monocytes of chronic hepatitis C patients were significantly higher than those of healthy individuals (P < 0.01). An inhibition of Notch signaling pathway with DAPT had reduced the relative expression level of TLR4 mRNA (2.58 ± 1.36 vs. 4.34 ± 1.88, P < 0.05), protein expression and phosphorylation of NF-B in CD14+ monocytes of chronic hepatitis C patients. Furthermore, the secretion level of MCP-1 [(94.32 ± 23.59) pg/ml vs. (64.07 ± 9.39) pg/ml, P < 0.01] and IL-8 [(12.54 ± 4.89) pg/ml vs. (7.92 ± 3.01) pg/ml, P < 0.05] was significantly reduced. TLR4 siRNA transfection reduced the expressions of Notch1 mRNA (2.09 ± 1.72 vs. 3.73 ± 1.75, P < 0.05), Hes1 (2.87 ± 0.84 vs. 5.54 ± 0.97, P < 0.01), and Hes5 (2.89 ± 0.93 vs. 4.51 ± 1.54, P < 0.01) in CD14+ monocytes of chronic hepatitis C patients.
Conclusion:Interaction of Notch signaling pathway with TLR4 can promote the function of CD14+ monocytes in chronic hepatitis C patients.
