Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells.
Mucus hypersecretion associated with airway inflammation is reduced by glucocorticoids. Two mechanisms of glucocorticoid-mediated inhibition of mucus production have been proposed, direct inhibition of mucus production by airway epithelial cells and indirectly through inhibition of proinflammatory mediators that stimulate mucus production. In this study, we examined the effect of dexamethasone (DEX) on mRNA expression and synthesis of MUC5AC by A549 human lung adenocarcinoma cells as well as Muc5ac and total high-molecular-weight (HMW) mucins by primary rat tracheal surface epithelial (RTSE) cells. Our results showed that in primary RTSE cells, DEX 1) dose dependently suppressed Muc5ac mRNA levels, but the levels of cellular Muc5ac protein and HMW mucins were unaffected; 2) did not affect constitutive or UTP-stimulated mucin secretion; 3) enhanced the translation of Muc5ac; and 4) increased the stability of intracellular Muc5ac protein by a mechanism other than the inhibition of the proteasomal degradation. In A549 cells, however, DEX suppressed both MUC5AC mRNA levels and MUC5AC protein secretion in a dose-dependent manner. We conclude that whereas DEX inhibits the levels of Muc5ac mRNA in primary RTSE cells, the levels of Muc5ac protein remain unchanged as a consequence of increases in both translation and protein stability. Interestingly, some of the effects of DEX were opposite in a cell line.
Lu
Wenju
W
Dept. of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA.
Lillehoj
Erik P
EP
Kim
K Chul
KC
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D055271:Mucin 5AC; D009077:Mucins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D005938:Glucocorticoids; C524678:MUC5AC protein, human; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D003907:Dexamethasone