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Am J Physiol Lung Cell Mol Physiol (March 12, 2004). doi:10.1152/ajplung.00047.2003
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Submitted on February 19, 2003
Accepted on March 8, 2004

Effects of Matrix Metalloproteinase Inhibitor on LPS-induced Goblet Cell Metaplasia

Je Hyeong Kim1, Sung Yong Lee2, Sang Myeon Bak3, In Bum Suh4, Sang Yeub Lee5, Chol Shin1, Jae Jeong Shim2, Kwang Ho In5, Kyung Ho Kang2, and Se Hwa Yoo5*

1 Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea, Republic of
2 Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea, Republic of
3 Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea, Republic of
4 Department of Clinical Pathology, Kangwon National University College of Medicine, Chuncheon, Korea, Republic of
5 Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea, Republic of

* To whom correspondence should be addressed. E-mail: yoosh47{at}unitel.co.kr.

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. And, 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 the 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, rats were treated 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 stainings 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, EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.




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