STUDIES ON VAGINAL INNATE IMMUNITY IN THE EPIVAGINAL MODEL SYSTEM.

As stated in the “Conclusions” section, this study by MatTek Corp. scientists demonstrated that the EpiVaginal human ectocervical-vaginal tissue equivalent provided valuable information on molecular mechanisms of vaginal innate immunity, and served as a test system to determine the effects of microbicides on vaginal immune defense. Background: The MatTek EpiVaginal tissue model, grown on tissue culture inserts from primary ectocervical epithelial and fibroblast cells, stratifies to resemble the normal human vaginal epithelium. Methodology: Scientists used a combination of RT-PCR, immunohistology and Bioplex/ELISA techniques to characterize innate immune responses in the EpiVaginal model and compare them to those of normal human vaginal tissues. Results: SLPI is abundantly expressed in both tissues; our earlier studies showed that concentrations of SLPI are decreased in women following the use of vaginal products such as nonoxynol-9 which cause inflammation. In EpiVaginal cultures, SLPI expression is downregulated by treatment with N-9, and by TNF-a alone. EpiVaginal cultures express low to negligible levels of the antimicrobial factors lysozyme and lactoferrin under normal conditions, but are capable of absorbing these factors from human seminal plasma, which contains high concentrations of both lysozyme and lactoferrin. Both EpiVaginal and normal tissues express toll-like receptors (TLRs)-1,2,3,5 and 6, as detected by RT-PCR; stimulation of EpiVaginal cultures with ligands that activate these TLRs induces directional secretion of the chemokines IL-8 and RANTES, as well as IL-6 and G-CSF, into the lower culture chambers. Conclusion: These findings indicate that the EpiVaginal model can provide valuable information on molecular mechanisms of vaginal innate immunity, and serve as a test system to determine effects of microbicides on vaginal immune defense.

Anti-microbial, Anti-microbial factor, Antimicrobial, Antimicrobial factor, EpiVaginal, G-CSF, IL-6, IL-8, Innate immunity, Lactoferrin, Lysozyme, Microbicide, Microbicides, Nonoxynol-9, RANTES, SLPI, TLR, TNF-a, Toll-like receptors, Vaginal innate immunity