GCs inhibited MUC5AC production induced by TGF-α alone or a combination of TGF-α and polyI:C; the repression may be mediated at the transcriptional but not post-transcriptional level.

Mucous secretion from airway epithelium plays a pivotal role in primary immune response against pathogens which infect the airway. However its excessive secretion can cause obstruction of airways and respiratory failure. Therefore it is vital to understand mechanisms underlying mucous secretion from airway epithelium and develop medical strategy to control the production of mucous. We have developed an in vitro viral-induced mucin production model using human airway epithelial cell line, NCI-H292, and found that TGF-α and double stranded RNA, polyI:C synergistically induce expression of MUC5AC (J Immunol 2009). Here we uncover IFN-γ suppresses transcription of MUC5AC induced by TGF-α and polyI:C in H292 cells and reveal its molecular mechanisms. IFN-γ inhibited activation of ERK1/2 provoked by TGF-a and polyI:C 9-12 hours after stimulation. IFN-γ decreased TGF-α and polyI:C-upregulated SP1 binging to its cognate site of the MUC5AC promoter. By using inhibitors against SP1 and ERK1/2 phosphorylation, we found that ERK1/2 activation and SP1 binding is independent from each other. These findings demonstrate IFN-g suppress dual pathways that are required for MCU5AC expression.