Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells.

ABSTRACT

PROBLEM: Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown. METHOD OF STUDY Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E2), progesterone (P4) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity. RESULTS: E2 significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E2 -treated cells had no anti-HIV activity, while that from E2 /P4 -treated cells significantly inhibited HIV-BaL infection. CONCLUSION: The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E2, suggesting that innate immune protection varies in the vagina across the menstrual cycle.