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Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease.

Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease.
Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease.
Background: In both ulcerative colitis (UC) and Crohn's disease (CD) there is a marked increase in mucosal IgG plasma cells (PC), although their precise role is not well established. In this study we isolated gut PCs from patients with IBD and normal controls and analyzed cytokine production, matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 production, and PC longevity ex vivo.Methods: Lamina propria mononuclear cells (LPMCs) were isolated from patients with CD (n = 19), UC (n = 27), and normal controls (n = 42). PCs were further selected by immunomagnetic isolation using CD138 microbeads. Cytokine, MMP-3, and TIMP-1 expression was investigated by Taqman polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and confocal microscopy. PC lifespan in vitro was studied by ELISpot analysis.Results: PCs from both controls and IBD patients contained high levels of transcripts for TGFbeta, whereas they did not contain significant transcripts for IL-4, IL-5, IL-10, IFNgamma, TNF, or IL-12p40. PCs from patients with CD and UC expressed significantly higher levels of MMP-3 protein and transcripts than controls (P < 0.0001). The vast majority of MMP-3-expressing PCs were IgG+ve. In culture, IgA PCs from both IBD patients and controls persisted for only a few days, but IgG PCs from IBD patients persisted for at least 3 weeks.Conclusions: We have demonstrated that IgG PCs from patients with IBD express large amounts of MMP-3 and that they appear to be long-lived. These results identify a new pathway by which IgG PCs may damage the gut.(Inflamm Bowel Dis 2007).
Crohn's disease, cytokines, matrix metalloproteinase, plasma cell, ulcerative colitis
195-203
Gordon, John N.
3f07dd32-289a-46a8-9ad3-d2ad2b1592d3
Pickard, Karen M.
e5188669-dff1-49c7-9c6f-8122b0c74bd9
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Prothero, Joanna D.
93bbda3a-fe63-4b42-8c27-6bd3ad0fa567
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Goggin, Patrick M.
7cf53c28-7b1c-4737-b500-5746f71e0254
MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816
Gordon, John N.
3f07dd32-289a-46a8-9ad3-d2ad2b1592d3
Pickard, Karen M.
e5188669-dff1-49c7-9c6f-8122b0c74bd9
Di Sabatino, Antonio
08cb3ec3-e4a0-423c-aa27-f428979b957d
Prothero, Joanna D.
93bbda3a-fe63-4b42-8c27-6bd3ad0fa567
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Goggin, Patrick M.
7cf53c28-7b1c-4737-b500-5746f71e0254
MacDonald, Thomas T.
a6bde8a9-acc4-4128-851f-dd5dbfe28816

Gordon, John N., Pickard, Karen M., Di Sabatino, Antonio, Prothero, Joanna D., Pender, Sylvia L.F., Goggin, Patrick M. and MacDonald, Thomas T. (2008) Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease. Inflammatory Bowel Disease, 14 (2), 195-203. (doi:10.1002/ibd.20302).

Record type: Article

Abstract

Background: In both ulcerative colitis (UC) and Crohn's disease (CD) there is a marked increase in mucosal IgG plasma cells (PC), although their precise role is not well established. In this study we isolated gut PCs from patients with IBD and normal controls and analyzed cytokine production, matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 production, and PC longevity ex vivo.Methods: Lamina propria mononuclear cells (LPMCs) were isolated from patients with CD (n = 19), UC (n = 27), and normal controls (n = 42). PCs were further selected by immunomagnetic isolation using CD138 microbeads. Cytokine, MMP-3, and TIMP-1 expression was investigated by Taqman polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and confocal microscopy. PC lifespan in vitro was studied by ELISpot analysis.Results: PCs from both controls and IBD patients contained high levels of transcripts for TGFbeta, whereas they did not contain significant transcripts for IL-4, IL-5, IL-10, IFNgamma, TNF, or IL-12p40. PCs from patients with CD and UC expressed significantly higher levels of MMP-3 protein and transcripts than controls (P < 0.0001). The vast majority of MMP-3-expressing PCs were IgG+ve. In culture, IgA PCs from both IBD patients and controls persisted for only a few days, but IgG PCs from IBD patients persisted for at least 3 weeks.Conclusions: We have demonstrated that IgG PCs from patients with IBD express large amounts of MMP-3 and that they appear to be long-lived. These results identify a new pathway by which IgG PCs may damage the gut.(Inflamm Bowel Dis 2007).

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e-pub ahead of print date: 16 November 2007
Published date: February 2008
Keywords: Crohn's disease, cytokines, matrix metalloproteinase, plasma cell, ulcerative colitis
Organisations: Faculty of Medicine, Cancer Sciences

Identifiers

Local EPrints ID: 59305
URI: https://eprints.soton.ac.uk/id/eprint/59305
PURE UUID: 43a04a1e-ea03-410a-a0db-cc2af4a06a50
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333

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Date deposited: 08 Sep 2008
Last modified: 20 Jul 2019 01:06

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Contributors

Author: John N. Gordon
Author: Karen M. Pickard
Author: Antonio Di Sabatino
Author: Joanna D. Prothero
Author: Patrick M. Goggin
Author: Thomas T. MacDonald

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