Production of antimicrobial peptides by human uterine epithelial cells and their regulation by prostaglandin E2
Chenoweth, Elizabeth M.
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Epithelial cells defend against pathogens not only by serving as a protective physical barrier, but also by actively producing antimicrobial peptides (AMPs). Few AMPs have been isolated from epithelial cells of the human female reproductive tract (FRT), and even fewer from uterine epithelial cells (UECs). Knowledge of AMP production and regulation would greatly increase our understanding of immune responses to diseases within the FRT. This study was prompted by recent deaths due to rare Clostridium sordellii infections following medical abortions using misoprostol, an analogue of the lipid mediator prostaglandin E2 (PGE2). We hypothesized that misoprostol and PGE2 suppress the immune system by decreasing AMP production by UECs. We used real-time PCR to measure the presence and relative concentrations of various AMPs in unstimulated RL95-2 (derived from human endometrial carcinoma) cells, as well as in cells treated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) or TNF -α and PGE2. Unstimulated cells produced all tested AMPs. Several patterns of AMP production warrant further study, including increases and decreases in the concentration of AMPs induced by treatment with TNF-α and PGE2, respectively. Therefore, treatments and preventative measures that focus on increasing production of AMPs may be effective against various diseases of the FRT.