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Updated: Jul 24, 2025
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IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on
Chong Zhong Liu1, Xing Bao Liu2, Jun Sun1
1Department of Hepatobiliary Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, PR China.
Background:
CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function.
Methods:
Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression.
Results:
A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression.
Conclusions:
Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.
Insights
Interleukin 8 (IL-8) overexpression in hepatocellular carcinoma (HCC) patients reduces CXC-chemokine receptor 2 (CXCR2) on monocytes. A monoacylglycerol lipase (MAGL) inhibitor partially reverses this CXCR2 down-regulation.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- CXC-chemokine receptor 2 (CXCR2) is downregulated on circulating monocytes in cancer patients.
- This study investigates CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC).
Purpose of the Study:
- Analyze the percentage of CD14+CXCR2+ monocyte subsets in HCC patients.
- Investigate mechanisms regulating CXCR2 expression and function on monocytes.
Main Methods:
- Flow cytometry to quantify CD14+CXCR2+ monocytes.
- Measure Interleukin 8 (IL-8) levels and correlate with monocyte subsets.
- In vitro studies using THP-1 cells treated with IL-8, assessing CXCR2 expression, monocyte antitumor activity, and MAGL inhibitor effects.
Main Results:
- HCC patients showed a decreased proportion of CD14+CXCR2+ monocytes compared to controls.
- IL-8 was overexpressed in HCC patients, negatively correlating with CXCR2+ monocyte proportion.
- IL-8 decreased CXCR2 expression and antitumor activity; MAGL inhibitor partially reversed this.
Conclusions:
- IL-8 overexpression in HCC downregulates monocyte CXCR2 expression.
- Monoacylglycerol lipase (MAGL) inhibition offers a potential strategy to partially restore CXCR2 levels.
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