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Title 

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18

Authors 

Young Sik ChoJeong Woo KangMin Chul ChoCheong Weon ChoShin Je LeeYong Kyung ChoeYong Man KimIn Pyo ChoiSue Nie ParkSoo Hyun KimCharles A DinarelloDo Young Yoon

Publisher 

Elsevier

Issue Date 

2001

Citation 

FEBS Letters, vol. 501, no. 2, pp. 139-145

Keywords 

human papillomavirus E6 oncogeneinterleukin-18cervical cancerinterferon γinterleukin 18

Abstract 

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.

ISSN 

0014-5793

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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