title: Estrogen modulation of pneumonia? An immunoglobulin A effect.
abstract: BACKGROUND
  Laboratory and clinical studies demonstrated a salutary effect of estradiol (E2) on pneumonia and other infectious complications after trauma, while dihydrotestosterone (DHT) failed to show a similar effect. Secretory immunoglobulin A is the principle antibody in the respiratory and other mucosal secretions. Immunoglobulin A (IgA) production and transport into the mucosal secretion is regulated by Toll-like receptor 4 (TLR-4). In addition, E2 may influence immune regulatory cells via TLR-4. We hypothesized that the protective effect of E2 on the development of pneumonia may be related to modulation of IgA transport into respiratory secretions.
  
  
  METHODS
  Calu-3 respiratory epithelial cell monolayers were established in a two-chamber cell culture system. Calu-3 cells were then treated with either E2 or DHT for 3 days for maximal cell stimulation. Dimeric IgA was added to the basal chamber of Calu-3 cells, and IgA transcellular transport was indexed by recovery of secretory immunoglobulin A in the apical chamber media. In separate experiments, Klebsiella pneumonia (10(5) CFU/mL) was added to the apical chamber of treated Calu-3 cell monolayers, and bacterial passage across Calu-3 cells was determined by bacterial recovery from the basal chamber. Calu-3 cells not treated with E2 or DHT served as control.
  
  
  RESULTS
  Calu-3 cells pretreated with E2 significantly increased IgA transport, and this effect was augmented in a dose-dependent fashion. Only cells pretreated with E2 significantly decreased bacterial passage, and this effect was exhibited in a dose- and time-dependent fashion. E2 led to a significant increase in TLR-4 expression.
  
  
  CONCLUSIONS
  The protective effect of E2 against pneumonia may be related to augmented transport of IgA into the respiratory mucosal secretions.
authors.affiliation: Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Abubaker A
authors.initials: AA
authors.lastname: Ali
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Diebel
authors.forename: David M
authors.initials: DM
authors.lastname: Liberati
mesh_terms: D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000382:microbiology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007070:Immunoglobulin A / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007710:Klebsiella Infections / Q000188:drug therapy / Q000276:immunology; D007711:Klebsiella pneumoniae; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000503:physiopathology; D012137:Respiratory System / Q000166:cytology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D051197:Toll-Like Receptor 4; D013196:Dihydrotestosterone; D004958:Estradiol