Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn's disease phenotype.
OBJECTIVE
Matrix metalloproteinases are associated with matrix turnover in both physiological and pathological conditions. We postulate an association between aberrant matrix metalloproteinases proteolytic activity and the intestinal tissue destruction, seen in patients with Crohn's disease and/or ulcerative colitis.


METHODS
Surgically resected inflamed and non-inflamed ileum and colon with/without extensive fibrosis from 122 Crohn's disease, 20 ulcerative colitis and 62 control patients were homogenized. Protein levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured by enzyme-linked immunosorbent assays (ELISA), while matrix metalloproteinases and myeloperoxidase activity were measured by specific activity assays.


RESULTS
Expression of total levels of matrix metalloproteinases-1, -2, -3 and -9 relative to tissue inhibitor of metalloproteinases-1 and -2 was increased in inflamed inflammatory bowel disease compared to non-inflamed inflammatory bowel disease and control intestinal mucosa. Also, net matrix metalloproteinases-1, -2, -3 and -9 activity in inflamed inflammatory bowel disease was increased, with similar expression profiles in Crohn's disease and ulcerative colitis. Within inflamed inflammatory bowel disease, a close correlation of matrix metalloproteinases with myeloperoxidase was observed. The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases was similar in inflamed Crohn's disease tissue with or without extensive fibrosis and not related to fistulizing disease.


CONCLUSIONS
We have shown increased net matrix metalloproteinases activity in intestinal inflammatory bowel disease tissue, likely to contribute to the tissue damage and remodelling seen in inflammatory bowel disease.
Meijer
M J W
MJ
Department of Gastroenterology-Hepatology, C4P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Mieremet-Ooms
M A C
MA
van der Zon
A M
AM
van Duijn
W
W
van Hogezand
R A
RA
Sier
C F M
CF
Hommes
D W
DW
Lamers
C B H W
CB
Verspaget
H W
HW
D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
D015415:Biomarkers; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1