Role of the CXCR3‑mediated TLRs/MyD88 signaling pathway in promoting the development of hepatitis B into cirrhosis and liver cancer

Yuan,Gang; Chen,Bin; Meng,Yina; Lu,Jialin; Shi,Xiaojun; Hu,Airong; Hu,Yaoren; Wang,Donghui

doi:10.3892/mmr.2021.12378

Role of the CXCR3‑mediated TLRs/MyD88 signaling pathway in promoting the development of hepatitis B into cirrhosis and liver cancer

Authors:
- Gang Yuan
- Bin Chen
- Yina Meng
- Jialin Lu
- Xiaojun Shi
- Airong Hu
- Yaoren Hu
- Donghui Wang
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Affiliations: Department of Acute Infection, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China, Hepatology Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China, Institute of Hepatology, Ningbo University School of Medicine, Ningbo, Zhejiang 315211, P.R. China, Department of Hepato‑Oncology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China, Institute of Hepatology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China
Published online on: August 20, 2021 https://doi.org/10.3892/mmr.2021.12378
Article Number: 738
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑1β 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‑1β 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 α 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.

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