Does progesterone augment ureaplasma urealyticum-induced production of IL-8 by endocervical and vaginal epithelial cells?

Abstract

PRODUCTION OF IL-8 BY ENDOCERVICAL AND VAGINAL EPITHELIAL CELLS? MORGAN PELTIER, SIEW TEE, JOHN SMULIAN, University of Medicine and Dentistry of New Jersey, Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, New Jersey OBJECTIVE: Progesterone (P4) is known to have immunomodulatory activity in a variety of systems. Modulation of innate immunity in the lower genital tract by P4 may enhance a host response to vaginal pathogens associated with preterm birth, thereby improving defenses against these organisms. IL-8 is a key cytokine in the innate immune system. Therefore, we evaluated the effects of P4 on U. urealyticum-induced IL-8 production by vaginal and endocervical cell lines. STUDY DESIGN: Vaginal epithelial (VK2) and endocervical (END) cells were plated and treated with P4 or vehicle overnight. Heat-killed U. urealyticum was then added and cells were cultured for another overnight incubation. Conditioned medium was then assayed for IL-8. Two experiments were performed. In experiment A, 2 concentrations of U. urealyticum (0 or 11 CCU/ ml) were tested against 0, 1, 10, 100, 1000, and 10,000 ng/ml P4. For experiment B, 5 concentrations of U. urealyticum (0, 8, 9, 10 and 11 CCU/ml) were tested against 2 concentrations of P4 (0 and 10 ug/ml). RESULTS: END cells: For experiment A, U. urealyticum significantly increased IL-8 production (P=0.006). P4 increased IL-8 production at the highest concentration tested (P= 0.001). For experiment B, 10 ug/ml P4 increased IL-8 production by END cells at all levels of U. urealyticum tested. VK2 cells:IL-8 production by VK2 cells was significantly increased by bacteria (P=0.016) and P4 (P=0.016) for experiment A. However, the effect of P4 on IL-8 production was observed only for cultures not stimulated with U. urealyticum. For experiment B, P4 increased the production of IL-8 for unstimulated cultures of VK2 cells (P=0.005) and those treated with 8 CCU U. urealyticum (P=0.024). CONCLUSION: P4 enhances the production of IL-8 by vaginal and endocervical epithelial cells. Endocervical cells showed an especially strong IL-8 response to U. urealyticum, when pretreated with P4. This further supports the hypothesis that P4’s influence on local immunity of the cervix may play a role in protecting women against infection-mediated preterm birth.