Effect of dexamethasone and ACC on bacteria-induced mucin expression in human airway mucosa.
Gram-negative bacteria can stimulate mucin production, but excessive mucus supports bacterial infection and consequently leads to airway obstruction. Therefore, the effect of dexamethasone (DEX) and the antioxidant acetyl-cysteine (ACC) on bacteria-induced mucus expression was investigated. Explanted human airway mucosa and mucoepidermoid cells (Calu-3) were stimulated with lipopolysaccharide (LPS) or PAM3 (a synthetic lipoprotein). DEX or ACC were added to either LPS- or PAM3-stimulated airway mucosa or Calu-3 cells. Mucin mRNA expression (MUC5AC) and total mucus glycoconjugates (mucin protein) were quantified using real-time PCR and periodic acid Schiff staining. LPS and PAM3 significantly increased mucin expression in airway mucosa and Calu-3 cells (P < 0.05). DEX alone had no significant effect on mucin expression in airway mucosa or Calu-3 cells (P > 0.05). In contrast, DEX significantly reduced LPS- and PAM3-induced mucin expression in explanted mucosal tissue and mucin expression in Calu-3 cells (P < 0.05). In explanted human airway mucosa ACC alone significantly increased mucin expression (P < 0.05). In contrast, ACC significantly decreased LPS- and PAM3-induced mucin expression (P < 0.05). In Calu-3 cells ACC alone had no significant effect on mucin expression (P > 0.05). ACC decreased LPS- and PAM3-induced mucin expression, but this effect was not significant (P > 0.05). These data suggest that DEX can effectively reduce bacteria-induced mucin expression in the airways. ACC alone may increase mucin expression in noninfected mucosa, but it decreased bacteria-induced mucin expression. Further studies are warranted to evaluate whether the effect of DEX or ACC is clinically relevant.
Hauber
Hans-Peter
HP
Medical Clinic, Research Center Borstel, Research Center Borstel, Borstel, Germany. hphauber@web.de
Goldmann
Torsten
T
Vollmer
Ekkehard
E
Wollenberg
Barbara
B
Zabel
Peter
P
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008297:Male; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012475:Salmonella / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D008074:Lipoproteins; D009077:Mucins; D003907:Dexamethasone; D000111:Acetylcysteine