ORAL KERATINOCYTES IMMORTALIZED WITH THE EARLY REGION OF HUMAN PAPILLOMAVIRUS TYPE-16 SHOW ELEVATED EXPRESSION OF INTERLEUKIN-6, WHICH ACTSAS AN AUTOCRINE GROWTH-FACTOR FOR THE DERIVED T103C CELL-LINE

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by cells in re sponse to injurious stimuli including viral infections and UV light. N umerous human keratinocyte-derived lines overexpress IL-6 and have bee n 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 papillo mavirus (HPV) type 16 genomes, showed the highest levels of secretion. We have, therefore, asked whether immortalization of human keratinocy tes with HPV 16 could result in elevated secretion of IL-6. Oral kerat inocytes were transfected with a plasmid expressing the entire HPV typ e 16 early region under the control of the Moloney leukemia virus long terminal repeat promoter. Three immortal lines were derived and teste d for their ability to secrete biologically active IL-6. These lines s howed 2-, 3-, and 9-fold increases in detectable IL-6 when compared wi th parental strains of keratinocytes. Cells from one of these lines, T 103C, showed a negative growth response to IL-6-neutralizing antisera, suggesting that the secreted IL-6 acted as an autocrine growth stimul ator.