Differential expression of immunobiological mediators by immortalized human cervical and vaginal epithelial cells

We have recently generated human papillomavirus (HPV) 16/E6E7 immortalized epithelial cell lines from the human vagina, ectocervix, and endocervix to use in studies on the role of these cells in reproduction and immune defens e, The cell lines maintain the differentiation characteristics of their tis sues of origin: the endocervical cell line expresses characteristics of sim ple columnar epithelium, whereas the ectocervical and vaginal cell lines ex press characteristics of stratified squamous nonkeratinizing epithelia. As a first step in elucidating the role of these cells in immune defense, we h ave studied the expression of immunological mediators in nonstimulated and stimulated cultures. Without stimulation, all three lines consistently prod uced the cytokines macrophage colony-stimulating factor (M-CSF) and transfo rming growth factor beta 1, the chemokine interleukin (IL)-8, prostaglandin E-2, the secretory leukoproteinase inhibitor, and the polymeric immunoglob ulin receptor. The endocervical cell line, but not the others, also produce d the lymphopoietic cytokines IL-6, IL-7, and consistently detectable level s of the chemokine known as "regulated-upon-activation, normal T cell expre ssed and secreted" (RANTES). Stimulation with the exogenous cytokines inter feron gamma and tumor necrosis factor alpha induced or significantly up-reg ulated expression of several of the cytokines and chemokines (i.e., IL-6, I L-8, RANTES, and M-CSF), as well as major histocompatibility complex (MHC) class II antigens, and membrane expression and shedding of the intercellula r adhesion molecule-1 in all three cell lines. These data provide further e vidence that epithelial cells in the lower human female genital tract parti cipate in immunological functions, that their activity is up-regulated by p roinflammatory/immune cytokines, and that epithelial cell immunological fun ctions vary at different anatomical sites in the genital tract.