Differential expression of matrix metal loproteinases and interleukin-8 during regeneration of human airway epithelium in vivo

被引:33
作者
Coraux, C [1 ]
Martinella-Catusse, C [1 ]
Nawrocki-Raby, B [1 ]
Hajj, R [1 ]
Burlet, H [1 ]
Escotte, SE [1 ]
Laplace, V [1 ]
Brembaut, P [1 ]
Puchelle, E [1 ]
机构
[1] CHU Maison Blanche, INSERM, UMR S 514, F-51092 Reims, France
关键词
airway epithelium regeneration; matrix metalloproteinases; IL-8; humanized airway xenograft;
D O I
10.1002/path.1757
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In many airway diseases, the airway epithelium is severely damaged and has to regenerate rapidly to restore its function. The regeneration process involves chronological steps of epithelial cell migration, proliferation, stratification, and differentiation. The present study has used an in vivo humanized airway xenograft model in nude mice that mimics the regeneration dynamics of human airway epithelium after severe injury, and human-specific molecular tools, to study the expression profiles of epithelial matrix metalloproteinases (MMPs)-7 and -9, of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and of the pro-inflammatory cytokine interleukin-8 (IL-8) during the different steps of human airway epithelium regeneration. It was found that during the cell migration and proliferation steps, airway epithelial cells expressed IL-8 at a high level, whereas airway epithelial pseudo-stratification and surface airway epithelial differentiation were associated with increased expression of MMPs and a progressive decrease in IL-8. Interestingly, immunohistochemical analysis revealed exclusive expression of MMPs at the apical part of the well -differentiated regenerated airway epithelium, and incubation of the regenerating epithelial cells with MMP inhibitors led to abnormal epithelial differentiation. These data provide new insight into the temporal expression of MMPs and IL-8 during the regeneration of airway epithelium and demonstrate the involvement of these factors during the different steps that lead to restoration of a well-differentiated and functional airway epithelium. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:160 / 169
页数:10
相关论文
共 48 条
[1]   Matrix metalloproteinase-9 in lung remodeling [J].
Atkinson, JJ ;
Senior, RM .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2003, 28 (01) :12-24
[2]   GROWTH-STIMULATION OF HUMAN KERATINOCYTES BY TISSUE INHIBITOR OF METALLOPROTEINASES [J].
BERTAUX, B ;
HORNEBECK, W ;
EISEN, AZ ;
DUBERTRET, L .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1991, 97 (04) :679-685
[3]   Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin [J].
Betsuyaku, T ;
Fukuda, Y ;
Parks, WC ;
Shipley, JM ;
Senior, RM .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (02) :525-535
[4]  
Buisson AC, 1996, J CELL PHYSIOL, V166, P413, DOI 10.1002/(SICI)1097-4652(199602)166:2<413::AID-JCP20>3.0.CO
[5]  
2-A
[6]   Induction of matrix metalloproteinase MMP-9 (92-kDa gelatinase) by retinoic acid in human neuroblastoma SKNBE cells:: Relevance to neuronal differentiation [J].
Chambaut-Guérin, AM ;
Hérigault, S ;
Rouet-Benzineb, P ;
Rouher, C ;
Lafuma, C .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (02) :508-517
[7]   Temporal and spatial expression of matrix metalloproteinases during wound healing of human corneal tissue [J].
Daniels, JT ;
Geerling, G ;
Alexander, RA ;
Murphy, G ;
Khaw, PT ;
Saarialho-Kere, U .
EXPERIMENTAL EYE RESEARCH, 2003, 77 (06) :653-664
[8]  
DEGRE M, 1971, ACTA PATHOLOG MICROB, VB 79, P129
[9]  
DUNLEVY JR, 1995, J CELL SCI, V108, P311
[10]   Matrilysin expression and function in airway epithelium [J].
Dunsmore, SE ;
Saarialho-Kere, UK ;
Roby, JD ;
Wilson, CL ;
Matrisian, LM ;
Welgus, HG ;
Parks, WC .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (07) :1321-1331