The inhibitory effect of the leukotriene receptor antagonist on leukotriene D4-induced MUC2/5AC gene expression and mucin secretion in human airway epithelial cells.
OBJECTIVE
Mucin gene expression and mucin production are markedly increased in inflammatory airway disorders such as asthma, chronic bronchitis and rhinosinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators such as prostaglandin and leukotriene are related to the secretion and production of mucin. However, the relationship of leukotrienes with mucin genes expression is not clear. The aim of this study is to evaluate MUC2/5AC gene expression and mucin secretion by the leukotriene receptor in human airway epithelial cells.


METHODS
The effect of leukotriene D(4) and the leukotriene receptor antagonist, pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and mucin secretion were observed in human airway NCI-H292 epithelial cells. The mRNA levels of MUC2/5AC and the amount of mucin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunoassay.


RESULTS
Leukotriene D(4) upregulated MUC2/5AC gene expression and mucin secretion in a dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 microM) downregulated the leukotriene D(4)-induced MUC2/5AC gene expression and mucin secretion.


CONCLUSIONS
These results suggest that the leukotriene receptor system is one of the mechanisms related to MUC2/5AC gene expression and mucin secretion in the human airway epithelium.
Bai
Chang Hoon
CH
Department of Otorhinolaryngology, College of Medicine, Yeungnam University, South Korea.
Song
Si-Youn
SY
Kim
Yong-Dae
YD
D018277:Carcinoma, Mucoepidermoid; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D008175:Lung Neoplasms; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D018077:Receptors, Leukotriene / Q000187:drug effects*; D020545:Respiratory Mucosa / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D002867:Chromones; D020024:Leukotriene Antagonists; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D018077:Receptors, Leukotriene; D017998:Leukotriene D4; C047681:pranlukast