Role of matrix metalloproteinase-9 in lipopolysaccharide-induced mucin production in human airway epithelial cells.

Matrix metalloproteinases (MMPs) have been found to be involved in the pathogenesis of inflammatory airway diseases. However, the role of MMPs in lipopolysaccharide (LPS)-induced mucin overproduction remains unclear. We explored the role of MMP-9 in LPS-induced MUC5AC production and the effect of doxycycline on MUC5AC production. The study showed that LPS induced transcription and protein expression of both MMP-9 and MUC5AC in NCI-H292 cells and in primary human epithelial cells, and the increased MUC5AC level were associated with increased MMP-9 transcripts, protein and activity. However, the increase of MUC5AC transcripts and protein were diminished after cells had been treated with doxycycline, MMP-9 siRNA or EGFR inhibitor. Doxycycline inhibited MMP-9 transcription, protein production and activity, while LPS-induced increase of MMP-9 transcription was inhibited by EGFR inhibitor, p38 MAPK and JNK inhibitor. The LPS-induced phosphorylation of p38 MAPK and JNK were inhibited by EGFR inhibitor. These results suggested that LPS-induced MUC5AC production may be partially mediated by MMP-9 activation and EGFR-p38 MAPK/JNK signaling pathway. Doxycycline may play a therapeutic role in LPS-induced mucus hypersecretion.