Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia.
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.
Kim
Je Hyeong
JH
Department of Internal Medicine, Korea University Ansam Hospital, Republic of Korea.
Lee
Sung Yong
SY
Bak
Sang Myeon
SM
Suh
In Bum
IB
Lee
Sang Yeub
SY
Shin
Chol
C
Shim
Jae Jeong
JJ
In
Kwang Ho
KH
Kang
Kyung Ho
KH
Yoo
Se Hwa
SH
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*
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