Stromelysin-1 and macrophage metalloelastase expression
in the intestinal mucosa of Crohn’s disease patients treated
with infliximab
Stromelysin-1 and macrophage metalloelastase expression
in the intestinal mucosa of Crohn’s disease patients treated
with infliximab
Background and aims: the mechanism by which
anti-tumor necrosis factor (TNF)-a therapy promotes rapid
closure of fistulas and mucosal wound healing in Crohn’s
disease (CD) remains unclear. An ex-vivo model of gut
T-cell mediated injury indicated that TNF-a blockade
prevents tissue damage concomitant with matrix
metalloproteinase (MMP) inhibition. We, therefore,
hypothesized that the chimeric anti-TNF-a antibody
infliximab facilitates wound healing in CD by
downregulating tissue degrading MMPs. We focused
on MMP-3 (stromelysin-1) and MMP-12 (macrophage
metalloelastase) as these two enzymes have been linked
to connective tissue destruction in CD.
Methods: endoscopic biopsies were taken from
10 CD patients immediately before and after 10 weeks of
treatment with infliximab. Before treatment, biopsies were
taken from macroscopically inflamed areas, and after
treatment were collected from the same locations as
before treatment. The degree of mucosal damage was
assessed by using a histological scoring system. MMP
transcripts were detected by in-situ hybridization on
paraffin sections. MMP proteins were determined by
immunoblotting on mucosal homogenates.
Results: six out of 10 patients had a clinical response
to infliximab. MMP-3 and MMP-12 transcripts and proteins,
which were highly expressed in CD inflamed mucosa,
decreased after treatment in those patients who responded to infliximab. MMP-3 and MMP-12
downregulation was accompanied by a concomitant
improvement of the histologic score. No change in
MMP expression was found in nonresponders.
Conclusion: the downregulation of tissue degrading
MMPs in CD mucosa may explain the wound
repair capacity of infliximab in healing fistulas and
ulcers.
1049-1055
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Saarialho-Kere, Ulpu
d3a10378-4e3e-45ee-86c4-c9ba28dd1522
Buckley, Mark G.
e4abc0c1-8413-4b27-bded-e94312c66424
Gordon, John N.
3f07dd32-289a-46a8-9ad3-d2ad2b1592d3
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Rovedatti, Laura
93ed44df-98f8-4ea2-bc64-de8b0e64d3c7
Corazza, Gina R.
f6c77bfb-9866-449c-882e-f72746f1009e
MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
September 2009
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Saarialho-Kere, Ulpu
d3a10378-4e3e-45ee-86c4-c9ba28dd1522
Buckley, Mark G.
e4abc0c1-8413-4b27-bded-e94312c66424
Gordon, John N.
3f07dd32-289a-46a8-9ad3-d2ad2b1592d3
Biancheri, Paolo
479c256d-187d-4b65-b226-8069299e61b2
Rovedatti, Laura
93ed44df-98f8-4ea2-bc64-de8b0e64d3c7
Corazza, Gina R.
f6c77bfb-9866-449c-882e-f72746f1009e
MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Di Sabatino, Antonio, Saarialho-Kere, Ulpu, Buckley, Mark G., Gordon, John N., Biancheri, Paolo, Rovedatti, Laura, Corazza, Gina R., MacDonald, Thomas T. and Pender, Sylvia L.F.
(2009)
Stromelysin-1 and macrophage metalloelastase expression
in the intestinal mucosa of Crohn’s disease patients treated
with infliximab.
European Journal of Gastroenterology & Hepatology, 21 (9), .
(doi:10.1097/MEG.0b013e3283293d0f).
Abstract
Background and aims: the mechanism by which
anti-tumor necrosis factor (TNF)-a therapy promotes rapid
closure of fistulas and mucosal wound healing in Crohn’s
disease (CD) remains unclear. An ex-vivo model of gut
T-cell mediated injury indicated that TNF-a blockade
prevents tissue damage concomitant with matrix
metalloproteinase (MMP) inhibition. We, therefore,
hypothesized that the chimeric anti-TNF-a antibody
infliximab facilitates wound healing in CD by
downregulating tissue degrading MMPs. We focused
on MMP-3 (stromelysin-1) and MMP-12 (macrophage
metalloelastase) as these two enzymes have been linked
to connective tissue destruction in CD.
Methods: endoscopic biopsies were taken from
10 CD patients immediately before and after 10 weeks of
treatment with infliximab. Before treatment, biopsies were
taken from macroscopically inflamed areas, and after
treatment were collected from the same locations as
before treatment. The degree of mucosal damage was
assessed by using a histological scoring system. MMP
transcripts were detected by in-situ hybridization on
paraffin sections. MMP proteins were determined by
immunoblotting on mucosal homogenates.
Results: six out of 10 patients had a clinical response
to infliximab. MMP-3 and MMP-12 transcripts and proteins,
which were highly expressed in CD inflamed mucosa,
decreased after treatment in those patients who responded to infliximab. MMP-3 and MMP-12
downregulation was accompanied by a concomitant
improvement of the histologic score. No change in
MMP expression was found in nonresponders.
Conclusion: the downregulation of tissue degrading
MMPs in CD mucosa may explain the wound
repair capacity of infliximab in healing fistulas and
ulcers.
This record has no associated files available for download.
More information
Published date: September 2009
Identifiers
Local EPrints ID: 72614
URI: http://eprints.soton.ac.uk/id/eprint/72614
ISSN: 0954-691X
PURE UUID: c06dfbc8-8292-4f20-abd2-7a09b21379ef
Catalogue record
Date deposited: 18 Feb 2010
Last modified: 14 Mar 2024 02:45
Export record
Altmetrics
Contributors
Author:
Antonio Di Sabatino
Author:
Ulpu Saarialho-Kere
Author:
Mark G. Buckley
Author:
John N. Gordon
Author:
Paolo Biancheri
Author:
Laura Rovedatti
Author:
Gina R. Corazza
Author:
Thomas T. MacDonald
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics