Regulation of human airway mucins by acrolein and inflammatory mediators

Bronchitis, asthma, and cystic fibrosis, marked by inflammation and mucus h ypersecretion, can be caused or exacerbated by airway pathogens or irritant s including acrolein, an aldehyde present in tobacco smoke. To determine wh ether acrolein and inflammatory mediators alter mucin gene expression, stea dy-state mRNA levels of two airway mucins, MUC5AC and MUC5B, were measured (by RT-PCR) in human lung carcinoma cells (NCI-H292). MUC5AC mRNA levels in creased after greater than or equal to 0.01 nM acrolein, 10 mu M prostaglan din E-2 or 15-hydroxyeicosatetraenoic acid, 1.0 nM tumor necrosis factor-al pha (TNF-alpha), or 10 nM phorbol 12-myristate 13-acetate (a protein kinase C activator). In contrast, MUC5B mRNA levels, although easily detected, we re unaffected by these agonists, suggesting that irritants and associated i nflammatory mediators increase mucin biosynthesis by inducing MUC5AC messag e levels, whereas MUC5B is constitutively expressed. When transcription was inhibited, TNF-alpha exposure increased MUC5AC message half-life compared with control level, suggesting that transcript stabilization is a major mec hanism controlling increased MUC5AC message levels. Together, these finding s imply that irritants like acrolein can directly and indirectly (via infla mmatory mediators) increase airway mucin transcripts in epithelial cells.