Influence of VEGF-C/VEGFR3 signaling pathway on dendritic cells derived from peripheral blood of tumor patients
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Abstract:
Objective:To culture peripheral blood mononuclear cell (PBMC) derived DCs of cancer patients in vitro and investigate the effect of VEGF-C/VEGFR3 signaling pathway on the functions of DCs.Methods: DCs were cultured using GM-CSF and IL-4 co-stimulating method, and then induced by VEGF-C (VEGF-C-DC), LPS (LPS-DC) or LPS+VEGF-C (LPS+VEGF-C-DC), respectively; and immature DCs (imDCs) was used as control group. The expressions of CD80, CD83, VEGFR3 and TLR4 on DCs surface were evaluated by flow cytometry. The expression of VEGFR3 was detected by immunofluorescence method. The secretions of IL-6, TNF-α and IL-12 in different treatment groups were detected by ELISA method. Results: VEGFR3 was highly expressed in LPS-DC. The expressions of CD80 and CD83 on LPS-DC and LPS+VEGF-C-DC were much higher than that on imDC and VEGF-C-DC (18.56 % vs 8.52 %,P<005), and showed phenotypic characteristics of mature DCs. Moreover, compared with LPS-DC, the expression of TLR4 on LPS+VEGF-C-DC was down-regulated, and the secretion of IL-6, TNF-α and IL-12 in LPS+VEGF-C-DC supernatant were also decreased. Conclusion: The VEGF-C/VEGFR3 signaling pathway can decrease DCs cytokine secretion through down-regulating TLR4 expression and act as a negative regulator of DCs immune response.
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Project supported by the National Natural Science Foundation of China (No.81401888) and the Applied Basic Research Programs of Science and Technology Commission Foundation of Tianjin City (No. 13JCYBJC41400, No.14JCTPJC00476)