Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-γ production in human peripheral blood mononuclear and NK cells
Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-γ production in human peripheral blood mononuclear and NK cells
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DOI：
10.4049/jimmunol.167.1.497
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发表时间：
2001-07-01
影响因子：
4.4
通讯作者：
Yoon, DY
中科院分区：
文献类型：
--
作者：
Lee, SJ;Cho, YS;Yoon, DY
宫颈癌是世界范围内女性恶性肿瘤中的主要癌症，而人乳头瘤病毒（HPV）16是与人宫颈癌相关的最常见的病原体。本研究旨在探讨HPV诱导的宫颈癌细胞免疫逃逸的机制。用ELISA法检测了含HPV的宫颈癌细胞系SiHa和CaSki细胞外液中HPV癌蛋白E6和E7的存在。评估HPV 16癌蛋白E6和E7对IL-18产生IFN-γ的影响。E6和E7蛋白降低了原代PBMC和NK 0细胞系中IL-18诱导的IFN-γ产生。FACS分析显示，病毒癌蛋白降低了IL-18与NK 0细胞上其细胞表面受体的结合，而癌蛋白对IL-1与D10 S（鼠Th细胞D10.G4.1的亚克隆）上其表面IL-1受体的结合没有影响。体外拉下测定还揭示了病毒癌蛋白和IL-18竞争性地结合IL-18 R α链。这些结果表明，细胞外HPV 16 E6和E7蛋白可以通过抑制IL-18与其α-链受体的结合来抑制HPV病变中IL-18诱导的IFN-γ的局部产生。HPV癌蛋白下调IL-18诱导的免疫应答可能有助于病毒的发病机制或致癌作用。免疫学杂志，2001年。
Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-gamma by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-gamma production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R alpha -chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-gamma production locally in HPV lesions through inhibition of IL-18 binding to its a-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis. The Journal of Immunology, 2001.