IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.

Abstract

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.

• Authors: Chong Zhong Liu, Xing Bao Liu, Jun Sun, Chao Qun Yu, Jing Chun Yao, Zhong Liu, Jing Cheng Hao
• Journal: BMC cancer (BMC Cancer) Vol. 23 Issue 1 Pg. 626 (Jul 04 2023) ISSN: 1471-2407 [Electronic] England
• PMID: 37403022 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• CXCL8 protein, human
• CXCR2 protein, human
• Immunologic Factors
• Interleukin-8
• Lipopolysaccharide Receptors
• Monoacylglycerol Lipases
• MGLL protein, human

Topics

• Humans
• Ascites (metabolism)
• Carcinoma, Hepatocellular (pathology)
• Down-Regulation
• Immunologic Factors
• Interleukin-8 (metabolism)
• Lipopolysaccharide Receptors (metabolism)
• Liver Neoplasms (pathology)
• Monoacylglycerol Lipases (metabolism)
• Monocytes (pathology)