Authors

Zhenjuan Chen, Ni Fan, Mingzhong Sun#

Departments

Department of Hepatology, Qingdao Sixth People's Hospital

Abstract

Objective: To investigate the role of interleukin-23 (IL-23)/interleukin-23 receptor (IL-23R) in the transformation of chronic hepatitis B to hepatocellular carcinoma. 

Methods: Seven-week-old healthy C57BL/6J mice and HBV transgenic mice were selected to culture HBV transgenic mice in male and female cages. After mating, F1 mice were born. At 3 weeks, 1ml of tail venous blood was collected from F1 mice and centrifuged to detect the changes of serum inflammatory factors (interleukin-6, IL-23). The mice in the observation group were injected with IL-23R neutralizing antibody intraperitoneally at 5, 9 and 15 weeks, 40 ug per mouse for 3 weeks, twice a week. The mice in the control group were injected with equal volume phosphate injection. The expression of IL-23R in liver tumors was measured by immunofluorescence. To observe the changes of vascular endothelial growth factor (VEGF) levels before and after IL-23R blockade at the 9th week. HE staining was used to observe the growth of liver tumors in mice at different time. 

Results: After stimulation with HbsAg and HbcAg, the levels of IL-6 and IL-23 in healthy and infected mice increased significantly (P<0.05), and HbsAg and HbcAg could stimulate the secretion of IL-23 more significantly. IL-23R positive cells were mainly distributed in the infiltrated immune cells of tumor tissue. Flow cytometry showed that IL-23R was mainly expressed in CD45 positive cells. Compared with before blockade, the level of vascular endothelial growth factor in liver tissue of mice decreased significantly (P<0.05). At the 9th week, the liver structure of mice was normal, with normal arrangement of hepatic lobules and occasional punctate necrosis; at the 15th week, the size and shape of the liver changed and atypical hyperplasia nodules were found; at the 19th week, there were obvious atypical hyperplasia in the liver tissue of mice, and some of the mice had tumor nodules; at the 21st week, the liver of mice was found to be well-defined, moderately and highly differentiated swelling. Nodule. When IL-23R was blocked at the 5th and 9th weeks, the number of tumors in the liver tissue of mice decreased significantly at the 21st week and before the blockade, while at the 15th week, there was no significant change in the number of tumors in the liver tissue of mice before the blockade. 

Conclusion: IL-23/IL-23R plays a promoting role in the conversion of chronic hepatitis B into liver cancer.

Keywords

IL-23, IL-23R, chronic hepatitis B, liver cancer.

DOI:

10.19193/0393-6384_2019_6_465