Role Of The Cxcr3-Mediated Tlrs/Myd88 Signaling Pathway In Promoting The Development Of Hepatitis B Into Cirrhosis And Liver Cancer

Chronic hepatitis B can lead to liver cirrhosis and primary hepatocellular carcinoma. The present study aimed to investigate whether C-X-C motif chemokine receptor 3 (CXCR3) regulates the genes in Toll-like receptors (TLRs)/myeloid differentiation primary response protein 88 (MyD88) signaling pathway in the development of hepatitis B into cirrhosis and liver cancer in vitro. A hepatitis B virus (HBV) overexpression lentivirus was constructed and infected into a LX-2 cell line to obtain stable HBV-overexpressing cells (named HBV-LX-2 cells). The CXCR3 gene was knocked down using small interfering RNA in HBV-LX-2 cells. Cell Counting Kit-8 assays, cell scratch tests and flow cytometry were used to detect cell proliferation, migration and apoptosis, respectively. The levels of IL-1 beta and IL-6 in serum samples of patients with liver cancer were measured via ELISA, and the collagen content in liver cancer tissues was detected using Masson staining. Western blotting was used to detect the expression levels of proteins in the TLRs/MyD88 signaling pathway. Excessive fibrosis was identified in the liver cancer tissues, and the serum levels of IL-6 and IL-1 beta were abnormally increased in patients with liver cancer. It was found that interfering with CXCR3 inhibited cell proliferation and migration, as well as promoted the apoptosis of HBV-LX-2 cells. Moreover, interfering with CXCR3 inhibited the expression levels of collagen type I alpha 1 chain and the proteins in the TLRs/MyD88 pathway. In conclusion, CXCR3 knockdown could inhibit the expression levels of proteins in the TLR4/MyD88 signaling pathway, decrease cell proliferation and migration, and promote cell apoptosis, thus inhibiting the development of liver cirrhosis to liver cancer.