Effect of the STING pathway on inflammatory cytokine secretion and phagocytosis by peripheral blood monocytes in patients with hepatitis B cirrhosis

Yifan YANG; Wanwei DU; Xia WANG; Guangde YANG; Li LI; Juanjuan FU; Xiucheng PAN

doi:10.3969/j.issn.1001-5256.2023.09.013

Volume 39 Issue 9

Sep. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(9): 2117-2121

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Effect of the STING pathway on inflammatory cytokine secretion and phagocytosis by peripheral blood monocytes in patients with hepatitis B cirrhosis

DOI: 10.3969/j.issn.1001-5256.2023.09.013

Department of Infectious Diseases，The Affiliated Hospital of Xuzhou Medical University，Xuzhou，Jiangsu 221002，China

Research funding:

National Science and Technology Major Project during the 13th Five－Year Plan Period (2018ZX10302－206)

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Corresponding author: PAN Xiucheng， xzpxc68@126.com （ORCID： 0000－0001－9706－9458）
Received Date: 2022-12-13
Accepted Date: 2023-02-02
Published Date: 2023-09-19

Abstract

Abstract

Objective To investigate the effect of the STING pathway on the inflammatory cytokine secretion and phagocytosis by peripheral blood monocytes in patients with hepatitis B cirrhosis. Methods Peripheral venous whole blood samples were collected from 35 patients with hepatitis B cirrhosis who were hospitalized in department of infectious diseases and 10 individuals who underwent physical examination in physical examination center in the Affiliated Hospital of Xuzhou Medical University from May to October 2020， and peripheral blood monocytes were isolated and extracted. Patients with hepatitis B cirrhosis were divided into three groups： cyclic GMP－AMP （cGAMP）（n=12）， cGAMP+CCCP （n=12） and Control （n=11）. In vitro， the STING activator cGAMP and/or the STING inhibitor CCCP were added to monocyte culture medium， and ELISA was used to measure the levels of interferon－α （IFN－α）， interferon－β （IFN－β）， interleukin－6 （IL－6）， and tumor necrosis factor－α （TNF－α） in supernatant. In addition， the monocyte culture system containing cGAMP and/or CCCP was co－cultured with fluorescein－labeled Escherichia coli， and then flow cytometry was used to observe changes in the phagocytosis of monocytes. The independent－samples t test was used for comparison of continuous data between two groups； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. Results Compared with the peripheral blood monocytes treated by the inhibitor CCCP， the peripheral blood monocytes stimulated by cGAMP secreted significantly higher levels of IFN－α， IFN－β， IL－6， and TNF－α （all P<0.05）. Compared with the healthy group， the hepatitis B cirrhosis group had a significant reduction in the phagocytosis of E. coli by peripheral blood monocytes， with or without cGAMP/cGAMP+CCCP treatment （t=4.647， 2.790， and 2.504， all P<0.05）， and cGAMP or cGAMP+CCCP stimulation had no significant effect on the phagocytosis of E. coli by peripheral blood monocytes in the patients with hepatitis B cirrhosis （P>0.05）. Conclusion The activation of the STING pathway in peripheral blood monocytes is involved in the development of systemic inflammatory response in hepatitis B cirrhosis， and the activation of the STING pathway has no significant effect on the phagocytosis of bacteria by peripheral blood monocytes in hepatitis B cirrhosis.
- Liver Cirrhosis,
- Cytokines,
- Stimulator of Interferon Genes

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Effect of the STING pathway on inflammatory cytokine secretion and phagocytosis by peripheral blood monocytes in patients with hepatitis B cirrhosis

DOI: 10.3969/j.issn.1001-5256.2023.09.013