Influence of Lactic Acid on Endogenous and Viral RNA-Induced Immune Mediator Production by Vaginal Epithelial Cells

Abstract

To evaluate the influence of lactic acid on immune mediator release from vaginal epithelial cells. The human vaginal epithelial cell line, VK2/E6E7, was cultured in the presence or absence of physiological concentrations of lactic acid, and in the presence or absence of the viral Toll-like receptor 3 agonist, poly (inosinic acid:cytidylic acid). Supernatants were assayed by enzyme-linked immunosorbent assay (ELISA) for interleukin (IL)-1β, IL-6, IL-8, IL-23, transforming growth factor (TGF)-β and secretory leukocyte protease inhibitor. Vaginal epithelial cells spontaneously released IL-1β (25.9 pg/mL), IL-8 (1.0 ng/mL), TGF-β (175 pg/mL), and secretory leukocyte protease inhibitor (33.8 ng/mL). Only TGF-β production was marginally enhanced (49%) by addition of lactic acid alone. Poly (inosinic acid:cytidylic acid) by itself stimulated the release of IL-6 (305 pg/mL) and enhanced IL-8 production (2.8 ng/mL). The combination of poly (inosinic acid:cytidylic acid) and lactic acid markedly increased IL-8 production (5.0 ng/mL) and induced the release of IL-1β (96.2 pg/mL). The poly (inosinic acid:cytidylic acid)-mediated lactic acid effect on IL-1β and IL-8 release was abrogated when the lactic acid was neutralized or if acetic acid was substituted for lactic acid. Lactic acid enhances the release of selective mediators from vaginal epithelial cells and stimulates antiviral immune responses.