Mengya Zang1, Yuan Li2, Huan He1, Huiguo Ding3, Kun Chen1, Jun Du1, Taoyang Chen4, Zhiyuan Wu1, Hui Liu3, Dongmei Wang1, Jianqiang Cai5, Chunfeng Qu6. 1. State Key Laboratory of Molecular Oncology/Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 2. State Key Laboratory of Molecular Oncology/Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 3. Gastroenterology and Hepatology Department, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. 4. Qidong Liver Cancer Institute & Qidong People's Hospital, Qidong, Jiangsu Province 226200, China. 5. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 6. State Key Laboratory of Molecular Oncology/Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: quchf@cicams.ac.cn.
Abstract
Liver inflammation after chronic hepatitis B virus (HBV) infection is essential for hepatocellular carcinoma (HCC) development. We did a nested case-control study based on QBC chronic HBV infection cohort to identify HCC-related inflammatory cytokines. Serum levels of distinct Th-cell representative cytokines at varied periods before HCC diagnosis were determined in 50 HCC cases and 150 age- and gender-matched controls who did not develop HCC in 8-10 years. The individuals with HCC outcome had statistically higher serum levels of IL-23 than controls (P < 0.01). Further analysis in HCC tissues showed that CD14+ inflammatory macrophages were the major IL-23 producers. Monocytes-derived macrophages generated more amount of IL-23 after being stimulated with cell-associated HBV core antigen from damaged HBV-infected hepatocytes than the cells being stimulated with HBV-S and HBV e antigen, which are secreted from infected hepatocytes. IL-23 upregulated IL-23 receptor expressions on macrophages, enhanced macrophage-mediated angiogenesis. In HBV-transgenic (Alb1HBV) mice, administration of diethylnitrosamine induced more liver tumors than in wild-type mice. The livers of Alb1HBV mice had higher concentrations of IL-23 and vascular endothelial growth factor (VEGF) than the wild-type mice. Neutralizing IL-23 activity, diethylnitrosamine-treated Alb1HBV mice developed significantly less tumors and produced less VEGF, tumor angiogenesis was inhibited with dramatically decreased CD31+ cells within tumor mass (all P < 0.01). CONCLUSION: Persistent IL-23 generation of liver inflammatory macrophages responding to damaged hepatocytes after chronic HBV infection altered macrophage function for HCC promotion. Blocking IL-23 activity might be helpful for the intervention in chronic hepatitis B patients who had high risk to HCC.
Liver inflammation after chronic hepatitis B virus (HBV) infection is essential for hepatocellular carcinoma (HCC) development. We did a nested case-control study based on QBC chronic HBV infection cohort to identify HCC-related inflammatory cytokines. Serum levels of distinct Th-cell representative cytokines at varied periods before HCC diagnosis were determined in 50 HCC cases and 150 age- and gender-matched controls who did not develop HCC in 8-10 years. The individuals with HCC outcome had statistically higher serum levels of IL-23 than controls (P < 0.01). Further analysis in HCC tissues showed that CD14+ inflammatory macrophages were the major IL-23 producers. Monocytes-derived macrophages generated more amount of IL-23 after being stimulated with cell-associated HBV core antigen from damaged HBV-infected hepatocytes than the cells being stimulated with HBV-S and HBV e antigen, which are secreted from infected hepatocytes. IL-23 upregulated IL-23 receptor expressions on macrophages, enhanced macrophage-mediated angiogenesis. In HBV-transgenic (Alb1HBV) mice, administration of diethylnitrosamine induced more liver tumors than in wild-type mice. The livers of Alb1HBV mice had higher concentrations of IL-23 and vascular endothelial growth factor (VEGF) than the wild-type mice. Neutralizing IL-23 activity, diethylnitrosamine-treated Alb1HBV mice developed significantly less tumors and produced less VEGF, tumor angiogenesis was inhibited with dramatically decreased CD31+ cells within tumor mass (all P < 0.01). CONCLUSION: Persistent IL-23 generation of liver inflammatory macrophages responding to damaged hepatocytes after chronic HBV infection altered macrophage function for HCC promotion. Blocking IL-23 activity might be helpful for the intervention in chronic hepatitis Bpatients who had high risk to HCC.
Authors: Marcos Luiz Gaia Carvalho; Luiz Fábio Magno Falcão; Jeferson da Costa Lopes; Caio Cesar Henriques Mendes; Fábio Alves Olímpio; Vanessa do Socorro Cabral Miranda; Lais Carneiro Dos Santos; Daniel Dias Pinheiro de Moraes; Marcos Virgilio Bertonsin Filho; Luccas Delgado da Costa; Raimunda do Socorro da Silva Azevedo; Ana Cecília Ribeiro Cruz; Vanessa Costa Alves Galúcio; Lívia Caricio Martins; Maria Irma Seixas Duarte; Arnaldo Jorge Martins Filho; Jorge Rodrigues de Sousa; Pedro Fernando da Costa Vasconcelos; Juarez Antônio Simões Quaresma Journal: Cells Date: 2022-06-28 Impact factor: 7.666
Authors: Seth A Domfeh; Patrick W Narkwa; Osbourne Quaye; Kwadwo A Kusi; Gordon A Awandare; Charles Ansah; Alimatu Salam; Mohamed Mutocheluh Journal: BMC Complement Med Ther Date: 2021-06-02