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Title 

Both e6 and e7 oncoproteins of human papillomavirus 16 inhibit il-18-induced IFN-γ production in human peripheral blood mononuclear and NK cells

Authors 

Shin Je LeeYoung Sik ChoMin Chul ChoJung Hyun ShimKyung Ae LeeKwang Kjune KoYong Kyung ChoeSue Nie ParkTomoaki HoshinoSoo Hyun KimCharles A DinarelloDo Young Yoon

Publisher 

American Association of Immunologists

Issue Date 

2001

Citation 

Journal of Immunology, vol. 167, no. 1, pp. 497-504

Keywords 

cell surface receptorinterleukin 18cancer cell culturecell surfacecompetitive inhibitioncytokine productionenzyme linked immunosorbent assayextracellular fluidhumanhuman cell

Abstract 

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-γ by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-γ 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 α-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-γ production locally in HPV lesions through inhibition of IL-18 binding to its α-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

ISSN 

0022-1767

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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