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[摘要]：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 NCl-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. (C) 2009 Elsevier Inc. All rights reserved. |
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