| First Author | Zang M | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 12 | Pages | 3759-3770 |
| PubMed ID | 30292634 | Mgi Jnum | J:270560 |
| Mgi Id | MGI:6277446 | Doi | 10.1016/j.bbadis.2018.10.004 |
| Citation | Zang M, et al. (2018) IL-23 production of liver inflammatory macrophages to damaged hepatocytes promotes hepatocellular carcinoma development after chronic hepatitis B virus infection. Biochim Biophys Acta Mol Basis Dis 1864(12):3759-3770 |
| abstractText | 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 8-10years. 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. |
