Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies
- Autores
- 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.
- Año de publicación
- 2007
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Di Sabatino, Antonio. Universita Degli Studi Di Pavia; Italia
Fil: Pender, Sylvia L.F.. University of Southampton; Reino Unido
Fil: Jackson, Claire L.. University of Southampton; Reino Unido
Fil: Prothero, Joanna D.. University of Southampton; Reino Unido
Fil: Gordon, John N.. Royal Hampshire County Hospital; Reino Unido
Fil: Picariello, Lucia. Università degli Studi di Firenze; Italia
Fil: Rovedatti, Laura. Universita Degli Studi Di Pavia; Italia
Fil: Docena, Guillermo H.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina
Fil: Monteleone, Giovanni. Universita Tor Vergata; Italia
Fil: Rampton, David S.. The Royal London Hospital; Reino Unido
Fil: Tonelli, Francesco. Università degli Studi di Firenze; Italia
Fil: Corazza, Gino R.. Universita Degli Studi Di Pavia; Italia
Fil: MacDonald, Thomas T.. Barts and The London School of Medicine and Dentistry; Reino Unido - Materia
-
IBD
TNF
INFLIXIMAB
MYOFIBROBLAST - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/111027
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Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor AntibodiesDi Sabatino, AntonioPender, Sylvia L.F.Jackson, Claire L.Prothero, Joanna D.Gordon, John N.Picariello, LuciaRovedatti, LauraDocena, Guillermo H.Monteleone, GiovanniRampton, David S.Tonelli, FrancescoCorazza, Gino R.MacDonald, Thomas T.IBDTNFINFLIXIMABMYOFIBROBLASThttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Infliximab 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.Fil: Di Sabatino, Antonio. Universita Degli Studi Di Pavia; ItaliaFil: Pender, Sylvia L.F.. University of Southampton; Reino UnidoFil: Jackson, Claire L.. University of Southampton; Reino UnidoFil: Prothero, Joanna D.. University of Southampton; Reino UnidoFil: Gordon, John N.. Royal Hampshire County Hospital; Reino UnidoFil: Picariello, Lucia. Università degli Studi di Firenze; ItaliaFil: Rovedatti, Laura. Universita Degli Studi Di Pavia; ItaliaFil: Docena, Guillermo H.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Monteleone, Giovanni. Universita Tor Vergata; ItaliaFil: Rampton, David S.. The Royal London Hospital; Reino UnidoFil: Tonelli, Francesco. Università degli Studi di Firenze; ItaliaFil: Corazza, Gino R.. Universita Degli Studi Di Pavia; ItaliaFil: MacDonald, Thomas T.. Barts and The London School of Medicine and Dentistry; Reino UnidoW B Saunders Co-Elsevier Inc2007-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/111027Di 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; 137-1490016-50851528-0012CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016508507009262info:eu-repo/semantics/altIdentifier/doi/10.1053/j.gastro.2007.04.069info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:15Zoai:ri.conicet.gov.ar:11336/111027instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:17:16.119CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
title |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
spellingShingle |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies Di Sabatino, Antonio IBD TNF INFLIXIMAB MYOFIBROBLAST |
title_short |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
title_full |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
title_fullStr |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
title_full_unstemmed |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
title_sort |
Functional Modulation of Crohn’s Disease Myofibroblasts by Anti-Tumor Necrosis Factor Antibodies |
dc.creator.none.fl_str_mv |
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. |
author |
Di Sabatino, Antonio |
author_facet |
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. |
author_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
IBD TNF INFLIXIMAB MYOFIBROBLAST |
topic |
IBD TNF INFLIXIMAB MYOFIBROBLAST |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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. Fil: Di Sabatino, Antonio. Universita Degli Studi Di Pavia; Italia Fil: Pender, Sylvia L.F.. University of Southampton; Reino Unido Fil: Jackson, Claire L.. University of Southampton; Reino Unido Fil: Prothero, Joanna D.. University of Southampton; Reino Unido Fil: Gordon, John N.. Royal Hampshire County Hospital; Reino Unido Fil: Picariello, Lucia. Università degli Studi di Firenze; Italia Fil: Rovedatti, Laura. Universita Degli Studi Di Pavia; Italia Fil: Docena, Guillermo H.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina Fil: Monteleone, Giovanni. Universita Tor Vergata; Italia Fil: Rampton, David S.. The Royal London Hospital; Reino Unido Fil: Tonelli, Francesco. Università degli Studi di Firenze; Italia Fil: Corazza, Gino R.. Universita Degli Studi Di Pavia; Italia Fil: MacDonald, Thomas T.. Barts and The London School of Medicine and Dentistry; Reino Unido |
description |
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. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-07 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/111027 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 0016-5085 1528-0012 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/111027 |
identifier_str_mv |
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 0016-5085 1528-0012 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0016508507009262 info:eu-repo/semantics/altIdentifier/doi/10.1053/j.gastro.2007.04.069 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
W B Saunders Co-Elsevier Inc |
publisher.none.fl_str_mv |
W B Saunders Co-Elsevier Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
_version_ |
1844614124617596928 |
score |
13.070432 |