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Activation of the interleukin‐32 pro‐inflammatory pathway in response to human papillomavirus infection and over‐expressionof interleukin‐32 controls the expression of the humanpapillomavirus oncogene
Author(s) -
Lee Sojung,
Kim JungHee,
Kim Heejong,
Kang Jeong Woo,
Kim SooHyun,
Yang Young,
Kim Jinman,
Park JongSup,
Park SurNie,
Hong JinTae,
Yoon DoYoung
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2010.03377.x
Subject(s) - oncogene , cancer research , transfection , cancer , cytokine , cervical cancer , biology , interleukin , hpv infection , small interfering rna , medicine , microbiology and biotechnology , immunology , cell culture , cell cycle , genetics
Summary High‐risk variants of human papillomavirus (HPV) induce cervical cancer by persistent infection, and are regarded as the principal aetiological factor in this malignancy. The pro‐inflammatory cytokine interleukin‐32 (IL‐32) is present at substantial levels in cervical cancer tissues and in HPV‐positive cervical cancer cells. In this study, we identified the mechanism by which the high‐risk HPV‐16 E7 oncogene induces IL‐32 expression in cervical cancer cells. We used antisense transfection, over‐expression, or knock‐down of IL‐32 to assess the effects of the HPV‐16 E7 oncogene on IL‐32 expression in cervical cancer cells. Cyclo‐oxygenase 2 (COX‐2) inhibitor treatment was conducted, and the expression levels, as well as the promoter activities, of IL‐32 and COX‐2 were evaluated in human HPV‐positive cervical cancer cell lines. E7 antisense treatment reduced the expression levels and promoter activities of COX‐2, which is constitutively expressed in HPV‐infected cells. Constitutively expressed IL‐32 was also inhibited by E7 antisense treatment. Moreover, IL‐32 expression was blocked by the application of the selective COX‐2 inhibitor, NS398, whereas COX‐2 over‐expression resulted in increased IL‐32 levels. These results show that the high‐risk variant of HPV induces IL‐32 expression via E7‐mediated COX‐2 stimulation. However, E7 and COX‐2 were down‐regulated in the IL‐32γ over‐expressing cells and recovered by IL‐32 small interfering RNA, indicating that E7 and COX‐2 were feedback‐inhibited by IL‐32γ in cervical cancer cells.