Glucocorticoid regulation of the humoral immune system. Dexamethasone stimulation of secretory component in serum, saliva, and bile.
Dexamethasone, a potent synthetic glucocorticoid, has been shown to increase polymeric immunoglobulin A (IgA) and antigen-specific IgA antibody levels in serum. This response coincided with a decline in IgA and IgG levels in saliva and vaginal secretions after dexamethasone treatment. To investigate the mechanism(s) of glucocorticoid action responsible for the accumulation of polymeric IgA in serum, we undertook in the present study to determine whether dexamethasone alters the production of secretory component (SC). SC is the receptor responsible for transporting IgA from blood and tissues into bile and external secretions. Dexamethasone administered in vivo increased SC levels in serum in a dose- and time-dependent manner. When bile and saliva samples were analyzed, dexamethasone treatment increased saliva SC levels and the production rate of SC by the liver, but had a pronounced inhibitory effect on both bile and salivary levels of IgA. As judged by HPLC, the majority of SC in blood was associated with polymeric IgA and not with monomeric IgA. Immunoblots showed the presence of a 29/27K doublet band of SC in serum from control- and dexamethasone-stimulated rats. These findings indicate that the elevation of polymeric IgA levels in serum after dexamethasone treatment may be due to decreased clearance of IgA into bile. Further, it demonstrates that liver production rate of SC as well as saliva and serum SC levels increase with glucocorticoid treatment. This findings suggests that glucocorticoids, which are known to stimulate hepatocyte SC synthesis in vitro, increase SC levels in blood, possibly as SC fragments that are capable of binding polymeric IgA and retarding its clearance from blood to bile.
Wira
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Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Rossoll
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RM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001646:Bile / Q000378:metabolism*; D001769:Blood / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects*; D007070:Immunoglobulin A / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D012463:Saliva / Q000378:metabolism*; D012635:Secretory Component / Q000737:chemistry / Q000378:metabolism*
D005938:Glucocorticoids; D007070:Immunoglobulin A; D012635:Secretory Component