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Oral keratinocytes immortalized with the early region of human papillomavirus type 16 show elevated expression of interleukin 6, which acts as an autocrine growth factor for the derived T103C cell line.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by cells in response to injurious stimuli including viral infections and UV light. Numerous human keratinocyte-derived lines overexpress IL-6 and have been shown to respond to IL-6 as a mitogen. In a survey of such lines, we discovered that two lines, SiHa and Caski, which harbor human papillomavirus (HPV) type 16 genomes, showed the highest levels of secretion. We have, therefore, asked whether immortalization of human keratinocytes with HPV 16 could result in elevated secretion of IL-6. Oral keratinocytes were transfected with a plasmid expressing the entire HPV type 16 early region under the control of the Moloney leukemia virus long terminal repeat promoter. Three immortal lines were derived and tested for their ability to secrete biologically active IL-6. These lines showed 2-, 3-, and 9-fold increases in detectable IL-6 when compared with parental strains of keratinocytes. Cells from one of these lines, T103C, showed a negative growth response to IL-6-neutralizing antisera, suggesting that the secreted IL-6 acted as an autocrine growth stimulator.