Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract

Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner

“…However, the relative affinities of P 4 and MPA for the GR may be different in this cell line compared with other cell lines, as it has previously been shown that the concentration of GR determines the binding affinity of a ligand for the receptor (93). Moreover, as we have previously shown that P 4 and MPA differentially regulate cytokine gene expression in a cell-and promoter-specific manner (39), discrepancies between the results from this study and others using synthetic GRE-containing promoters in COS-1 cells, for example (11), may be due to either cell-or promoter-specific effects.…”

“…These cells were used as an in vitro cell culture model for mucosal immunity in the female ectocervical environment, as they closely resemble the characteristics of their tissue of origin and primary cells (39,47). An increase in pro-inflammatory cytokines such as IL-12 is critical for the progression of inflammation, although anti-inflammatory cytokines such as IL-10 control the course of the inflammatory process (45,(53)(54)(55)(56).…”

“…Cell Culture-The human Ect1/E6E7 ectocervical epithelial cell line was purchased from the ATCC and cultured and prepared as described previously (39,47). The MDA-MB-231 human breast cancer cell line was a generous gift from Prof.…”

“…MPA has previously been shown to regulate cytokine/ chemokine gene expression in epithelial cell lines of the female genital tract in a ligand-, promoter-, and cell-specific manner (39). The possibility thus exists that MPA may disrupt normal immune responses in the female genital tract, thereby influencing inflammation at this site.…”

Expression and Localization of P-Glycoprotein, Multidrug Resistance Protein 4, and Breast Cancer Resistance Protein in the Female Lower Genital Tract of Human and Pigtailed Macaque

“…Different regions of the genital tract have different thicknesses of the protective epithelial layers, and have varying types and amounts of submucosal immune cells. A differential response to the same immunologic stimuli has been reported, [19][20][21][22] and regionally dependent susceptibility to HIV-1 infection has been suggested among different parts of the lower genital tract. The endocervix as well as the transformation zone between the endocervix and ectocervix were more vulnerable to HIV-1 infection compared to the ectocervix and vagina as examined in a macaque model.…”