Estrogen modulation of pneumonia? An immunoglobulin A effect
AA Ali, LN Diebel, DM Liberati - Journal of Trauma and Acute …, 2012 - journals.lww.com
AA Ali, LN Diebel, DM Liberati
Journal of Trauma and Acute Care Surgery, 2012•journals.lww.comBACKGROUND: Laboratory and clinical studies demonstrated a salutary effect of estradiol
(E 2) 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, E 2 may influence immune regulatory cells via TLR-4. We hypothesized that …
(E 2) 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, E 2 may influence immune regulatory cells via TLR-4. We hypothesized that …
Abstract
BACKGROUND:
Laboratory and clinical studies demonstrated a salutary effect of estradiol (E 2) 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, E 2 may influence immune regulatory cells via TLR-4. We hypothesized that the protective effect of E 2 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 E 2 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 E 2 or DHT served as control.
RESULTS:
Calu-3 cells pretreated with E 2 significantly increased IgA transport, and this effect was augmented in a dose-dependent fashion. Only cells pretreated with E 2 significantly decreased bacterial passage, and this effect was exhibited in a dose-and time-dependent fashion. E 2 led to a significant increase in TLR-4 expression.
CONCLUSION:
The protective effect of E 2 against pneumonia may be related to augmented transport of IgA into the respiratory mucosal secretions.
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