The regulatory effect of interleukin-33 signaling pathway on monocytes in patients with hepatitis B virus-associated hepatocellular carcinoma

YANG Lu; ZHANG Lanfang; MENG Lijun; ZHU Yanli; KUAI Jun; LI Wenjing

doi:10.13431/j.cnki.immunol.j.20240021

Abstract：To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.