title: Estrogen supports urothelial defense mechanisms.
abstract: Epidemiological data imply a role of estrogen in the pathogenesis of urinary tract infections (UTIs), although the underlying mechanisms are not well understood. However, it is thought that estrogen supplementation after menopause decreases the risk of recurrent infections. We sought to investigate the influence of estrogen on host-pathogen interactions and the consequences for UTI pathogenesis. We analyzed urothelial cells from menstruating and postmenopausal women before and after a 2-week period of estrogen supplementation, and also studied the influence of estradiol during Escherichia coli UTI in a mouse infection model. Important findings were confirmed in two human urothelial cell lines. We identified two epithelial defense mechanisms modulated by estrogen. Estrogen induced the expression of antimicrobial peptides, thereby enhancing the antimicrobial capacity of the urothelium and restricting bacterial multiplication. In addition, estrogen promoted the expression and redistribution of cell-cell contact-associated proteins, thereby strengthening the epithelial integrity and preventing excessive loss of superficial cells during infection. These two effects together may prevent bacteria from reaching deeper layers of the urinary tract epithelium and developing reservoirs that can serve as a source for recurrent infections. Thus, this study presents some underlying mechanisms for the beneficial effect of estradiol after menopause and supports the application of estrogen in postmenopausal women suffering from recurrent UTI.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Lüthje
authors.forename: Hanna
authors.initials: H
authors.lastname: Brauner
authors.forename: Nubia L
authors.initials: NL
authors.lastname: Ramos
authors.forename: Amanda
authors.initials: A
authors.lastname: Ovregaard
authors.forename: Regine
authors.initials: R
authors.lastname: Gläser
authors.forename: Angelica Lindén
authors.initials: AL
authors.lastname: Hirschberg
authors.forename: Pontus
authors.initials: P
authors.lastname: Aspenström
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D001743:Urinary Bladder / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; D004967:Estrogens; D004958:Estradiol