Analysis of the impact of the interleukin-27 receptor on the initiation of the hepatocellular carcinoma development

• Turan Aghayev
• Elizaveta K. Titerina
• Marina V. Khoreva
• Ekaterina K. Koltsova
• Lyudmila V. Gankovskaya

Abstract

Introduction. Hepatocellular carcinoma (HCC) is the most common type of liver cancer with low survival rate due to late detection. The cytokine IL-27 plays a key role by activating STAT1 and STAT3 factors, influencing the development of HCC. Recent studies indicate the importance of the IL-27R signaling pathway in the control of innate cytotoxic cells, which may be relevant for the diagnosis and treatment of early-stage HCC.

Aim – to study the role of IL-27R signaling in the early stages of HCC development.

Material and methods. The study used laboratory mice with genetic modifications in the IL-27 receptor gene (Il27ra^–/– and Il27ra^+/–) intraperitoneally injected with diethylnitrosamine (DEN) to analyze hepatocyte apoptosis and proliferation. Quantitative analysis of neutrophils was carried out using flow cytometry. The level of proliferation was determined by staining samples for the Ki67 marker in liver sections, and TUNEL analysis of lysates was used to detect apoptosis. Analysis of phosphorylation of the transcription factor STAT3 in the liver of mice was carried out using the Western Blot. The expression level of Ifng and genes Il10, Retnla, Chil3l1, Cd44, associated with repair in mouse liver, was analyzed by real-time PCR.

Results. After 48 hours following DEN administration, Il27ra^–/– mice exhibited decreased levels of proliferation and apoptosis in the liver, as well as decreased neutrophil numbers. Within 24 hours after DEN administration, there was an increase in the expression of genes associated with tissue repair in the liver in Il27ra^–/– mice.

Conclusion. The results of the study indicate the influence of the IL-27 signaling pathway on inflammation, apoptosis and proliferation of hepatocytes, and liver repair processes, providing the opportunity to assess the prognosis of HCC development by measuring the level of IL-27 after a damaging effect on the liver.

Keywords:inflammation; hepatocellular carcinoma; liver cancer; interleukin-27 receptor

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