Document Detail


Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium.
MedLine Citation:
PMID:  19137636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond for MMP cleavage. HT-29 and DLD-1 expressed several MMPs and levels of MMP-3, -10 and -13 mRNA expression were increased significantly by tumour necrosis factor (TNF)-alpha exposure. Transcripts of MMP-1, -3, -7, -9, -10 and -12 were detected in CECs and all, except MMP12, at significantly increased levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly by a specific MMP inhibitor (GM 6001). A significant TNF-alpha-mediated increase in MMP enzyme activity was also detected in HT-29 cells in vitro. In conclusion, the expression of several MMPs as well as the level of functional MMPactivity is increased in CEC from patients with active IBD. The results suggest that MMPs released by the intestinal epithelium may be involved in the pathogenesis of IBD by promoting local mucosal damage.
Authors:
G Pedersen; T Saermark; T Kirkegaard; J Brynskov
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  155     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-09     Completed Date:  2009-02-20     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  257-65     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Herlev University Hospital, Herlev, Denmark. giped@dadlnet.dk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cell Line, Transformed
Cells, Cultured
Colon / drug effects,  enzymology*
Cytokines / pharmacology*
Female
Gene Expression Regulation, Enzymologic / drug effects
Humans
Inflammatory Bowel Diseases / enzymology*
Intestinal Mucosa / drug effects,  enzymology*
Male
Matrix Metalloproteinases / biosynthesis*,  genetics
Middle Aged
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction / methods
Young Adult
Chemical
Reg. No./Substance:
0/Cytokines; 0/RNA, Messenger; EC 3.4.24.-/Matrix Metalloproteinases
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