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Down modulation of IL‐18 expression by human papillomavirus type 16 E6 oncogene via binding to IL‐18
Author(s) -
Cho Young-Sik,
Kang Jeong-Woo,
Cho MinChul,
Cho Cheong-Weon,
Lee ShinJe,
Choe Yong-Kyung,
Kim YongMan,
Choi InPyo,
Park Sue-Nie,
Kim SooHyun,
Dinarello Charles A.,
Yoon Do-Young
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02652-7
Subject(s) - hacat , oncogene , cytokine , microbiology and biotechnology , cell culture , chemistry , immune system , cancer research , biology , cell , immunology , cell cycle , genetics , biochemistry
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.