Artículo
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies
Di Sabatino, Antonio; Pender, Sylvia L.F.; Jackson, Claire L.; Prothero, Joanna D.; Gordon, John N.; Picariello, Lucia; Rovedatti, Laura; Docena, Guillermo H.
; Monteleone, Giovanni; Rampton, David S.; Tonelli, Francesco; Corazza, Gino R.; MacDonald, Thomas T.
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
07/2007
Editorial:
W B Saunders Co-Elsevier Inc
Revista:
Gastroenterology
ISSN:
0016-5085
e-ISSN:
1528-0012
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Infliximab induces immune cell apoptosis by outside-to-inside signaling through transmembrane tumor necrosis factor-α (mTNF). However, in inflamed gut, myofibroblasts also produce TNF-α, and the affects of anti-TNF antibodies on these structural cells are unknown. We investigated the action of infliximab on apoptosis, the production of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP)-1, and migration of Crohn’s disease (CD) myofibroblasts. Methods: Colonic myofibroblasts were isolated from patients with active CD and controls. mTNF was evaluated by Western blotting and flow cytometry. Infliximab-treated myofibroblasts were analyzed for apoptosis by Annexin V staining and caspase-3. TIMP-1 and MMPs were measured by Western blotting, and fibroblast migration was assessed by using an in vitro wound-healing scratch assay. Results: CD myofibroblasts showed higher mTNF expression than control myofibroblasts. Infliximab had no effect on CD myofibroblast apoptosis, caspase-3 activation, and production of MMP-3 and MMP-12. However, infliximab induced a significant dose-dependent increase in TIMP-1 production, which was inhibited by the p38 mitogen-activated protein kinase inhibitor SB 203580. The anti-TNF agents adalimumab, etanercept, and p55 TNF-receptor–human IgG fusion protein also increased TIMP-1 production. The migration of CD myofibroblasts was enhanced significantly by infliximab and recombinant human TIMP-1, and infliximab-induced migration was inhibited by anti–TIMP-1 neutralizing antibody. Infliximab also decreased CD myofibroblast collagen production. Conclusions: Our findings show a novel therapeutic pathway for anti-TNF therapies in enhancing TIMP-1 production and myofibroblast migration, which may reduce MMP activity and facilitate the wound healing.
Palabras clave:
IBD
,
TNF
,
INFLIXIMAB
,
MYOFIBROBLAST
Archivos asociados
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Identificadores
Colecciones
Articulos(CIDCA)
Articulos de CENTRO DE INV EN CRIOTECNOLOGIA DE ALIMENTOS (I)
Articulos de CENTRO DE INV EN CRIOTECNOLOGIA DE ALIMENTOS (I)
Citación
Di Sabatino, Antonio; Pender, Sylvia L.F.; Jackson, Claire L.; Prothero, Joanna D.; Gordon, John N.; et al.; Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies; W B Saunders Co-Elsevier Inc; Gastroenterology; 133; 1; 7-2007; 137-149
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