title: Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia.
abstract: Bacterial infections of the lung are known to induce inflammatory responses, which lead to mucus hypersecretion. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and its activation. Furthermore, matrix metalloproteinases (MMPs), especially MMP-9, have been reported to promote the transmigration of activated neutrophils. In this study, we investigated the associations between lipopolysaccharide (LPS)-induced goblet cell (GC) metaplasia and EGFR expression and the effects of MMP inhibitor (MMPI). Various concentrations of LPS were instilled into the tracheas of pathogen-free Sprague-Dawley rats, and airways were examined at different times after LPS instillation. To examine the role of MMP-9, we treated rats 3 days before LPS instillation and daily thereafter with MMPI. Neutrophilic infiltration, Alcian blue/periodic acid-Schiff (AB/PAS) staining, and immunohistochemical staining for MUC5AC, EGFR, and MMP-9 were performed. The instillation of LPS increased AB/PAS and MUC5AC staining in time- and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia. The instillation of LPS into the trachea also induced neutrophilic infiltration and EGFR and MMP-9 expression in the airway epithelium, and MMPI was found to significantly prevent neutrophil recruitment, GC metaplasia, and EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.
authors.affiliation: Department of Internal Medicine, Korea University Ansam Hospital, Republic of Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Sang Myeon
authors.initials: SM
authors.lastname: Bak
authors.forename: In Bum
authors.initials: IB
authors.lastname: Suh
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Se Hwa
authors.initials: SH
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008679:Metaplasia; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D020556:Neutrophil Infiltration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013754:Tetracyclines / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D013754:Tetracyclines; C117155:tetracycline CMT-3; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9