Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer.

Abstract

Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)-17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line. IL-17 expression was investigated in 79 NSCLC tumor tissues by immunohistochemistry. Growth rate, IL-17 mRNA, and secreting protein levels were also examined in HPV 16/18 E6-transfected H1299 human NSCLC cells. Immunohistochemical data showed that 48.1% of lung tumors had IL-17 staining, which was significantly associated with patients' sex (P = .03), HPV infection (P = .002), and tumor stage (P = .03). Significant correlations of IL-17 with IL-6 (P < .001) and IL-17 with Mcl-1 (P < .001) expression were also observed. Cell growth rate was increased, and IL-17/Mcl-1 expression levels were elevated in HPV 16 E6-transfected H1299 cells. The transfected E6 oncoproteins can significantly up-regulate expression levels of IL-17 and antiapoptotic protein Mcl-1. The study suggests that HPV infection-induced IL-17 levels can stimulate Mcl-1 expression through the PI3K pathway and promote lung tumor cell progression through a p53- and IL-6-independent pathway.