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.