title: Role of matrix metalloproteinase-9 in lipopolysaccharide-induced mucin production in human airway epithelial cells.
abstract: 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.
authors.affiliation: Department of Pulmonary Medicine, Research Institute of Respiratory Disease, Fudan University, Zhongshan Hospital, Shanghai, PR China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.forename: Ka
authors.initials: K
authors.lastname: Li
authors.forename: Pinghai
authors.initials: P
authors.lastname: Zhang
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
mesh_terms: D017931:DNA Primers; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D009077:Mucins / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D009077:Mucins; D020780:Matrix Metalloproteinase 9