title: Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells.
abstract: The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus. This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES). Cells were treated with proinflammatory molecules and mimics of infection [lipopolysaccharide (LPS) and lipoteichoic acid (LTA)]. mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR. HBD1 mRNA was present at very low levels preventing conclusive study of its regulation. However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha. SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha. LPS had little effect on antimicrobial expression. However, there was a trend towards increased expression with LTA treatment for 4-8 h. Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment. These results suggest that in endometrium some natural antibiotics (e.g. SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g. HBD2) are inducible allowing maximal antimicrobial activity during infection. Natural antimicrobials will have an important role in endometrium in protecting against infection.
authors.affiliation: MRC Human Reproductive Sciences Unit and Department of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9ET, UK. a.king@hrsu.mrc.ac.uk
authors.forename: Anne E
authors.initials: AE
authors.lastname: King
authors.forename: Diana C
authors.initials: DC
authors.lastname: Fleming
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Kelly
mesh_terms: D002460:Cell Line; D004717:Endometrium / Q000378:metabolism* / Q000382:microbiology; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D014176:Protein Biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger / Q000187:drug effects; D053481:Secretory Leukocyte Peptidase Inhibitor; D013682:Teichoic Acids / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000096:biosynthesis*
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C009900:lipoteichoic acid; D007371:Interferon-gamma