Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel dise...

Autores
Docena, Guillermo H.; Rovedatti, L.; Kruidenier, L.; Fanning, A.; Leaky, N.A.B.; Knowles, C.H.; Lee, K.; Shanahan, F.; Nally, K.; McLean, P.G.; Di Sabatino, A.; MacDonald, T.T.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) characterized by chronic relapsing mucosal inflammation. Tumour necrosis factor (TNF)-α, a known agonist of the mitogen-activated protein kinase (MAPK) pathway, is a key cytokine in this process. We aimed first to determine whether p38 MAPK is activated in IBD inflamed mucosa, and then studied the effect of four different p38α inhibitory compounds on MAPK phosphorylation and secretion of proinflammatory cytokines by IBD lamina propria mononuclear cells (LPMCs) and organ culture biopsies. In vivo phospho-p38α and p38α expression was evaluated by immunoblotting on intestinal biopsies from inflamed areas of patients affected by Crohn's disease and ulcerative colitis, and from normal mucosa of sex- and age-matched control subjects. Both mucosal biopsies and isolated LPMCs were incubated with four different p38α selective inhibitory drugs. TNF-α, interleukin (IL)-1β and IL-6 were measured in the organ and cell culture supernatants by enzyme-linked immunosorbent assay. We found higher levels of phospho-p38α in the inflamed mucosa of IBD patients in comparison to controls. All the p38α inhibitory drugs inhibited p38α phosphorylation and secretion of TNF-α, IL-1β and IL-6 from IBD LPMCs and biopsies. Activated p38α MAPK is up-regulated in the inflamed mucosa of patients with IBD. Additionally, all the p38α selective inhibitory drugs significantly down-regulated the activation of the MAPK pathway and the secretion of proinflammatory cytokines.
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: Rovedatti, L.. Universita Degli Studi Di Pavia; Italia
Fil: Kruidenier, L.. No especifíca;
Fil: Fanning, A.. No especifíca;
Fil: Leaky, N.A.B.. No especifíca;
Fil: Knowles, C.H.. No especifíca;
Fil: Lee, K.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
Fil: Shanahan, F.. University College Cork; Irlanda
Fil: Nally, K.. University College Cork; Irlanda
Fil: McLean, P.G.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
Fil: Di Sabatino, A.. Universita Degli Studi Di Pavia; Italia
Fil: MacDonald, T.T.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
Materia
CROHN'S DISEASE
LAMINA PROPRIA MONONUCLEAR CELL
P38 INHIBITOR
TNF-Α
ULCERATIVE COLITIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/135376
Acceder
id CONICETDig_44267f8364f5510c78849a87e8acb267
oai_identifier_str oai:ri.conicet.gov.ar:11336/135376
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel diseaseDocena, Guillermo H.Rovedatti, L.Kruidenier, L.Fanning, A.Leaky, N.A.B.Knowles, C.H.Lee, K.Shanahan, F.Nally, K.McLean, P.G.Di Sabatino, A.MacDonald, T.T.CROHN'S DISEASELAMINA PROPRIA MONONUCLEAR CELLP38 INHIBITORTNF-ΑULCERATIVE COLITIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) characterized by chronic relapsing mucosal inflammation. Tumour necrosis factor (TNF)-α, a known agonist of the mitogen-activated protein kinase (MAPK) pathway, is a key cytokine in this process. We aimed first to determine whether p38 MAPK is activated in IBD inflamed mucosa, and then studied the effect of four different p38α inhibitory compounds on MAPK phosphorylation and secretion of proinflammatory cytokines by IBD lamina propria mononuclear cells (LPMCs) and organ culture biopsies. In vivo phospho-p38α and p38α expression was evaluated by immunoblotting on intestinal biopsies from inflamed areas of patients affected by Crohn's disease and ulcerative colitis, and from normal mucosa of sex- and age-matched control subjects. Both mucosal biopsies and isolated LPMCs were incubated with four different p38α selective inhibitory drugs. TNF-α, interleukin (IL)-1β and IL-6 were measured in the organ and cell culture supernatants by enzyme-linked immunosorbent assay. We found higher levels of phospho-p38α in the inflamed mucosa of IBD patients in comparison to controls. All the p38α inhibitory drugs inhibited p38α phosphorylation and secretion of TNF-α, IL-1β and IL-6 from IBD LPMCs and biopsies. Activated p38α MAPK is up-regulated in the inflamed mucosa of patients with IBD. Additionally, all the p38α selective inhibitory drugs significantly down-regulated the activation of the MAPK pathway and the secretion of proinflammatory cytokines.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; ArgentinaFil: Rovedatti, L.. Universita Degli Studi Di Pavia; ItaliaFil: Kruidenier, L.. No especifíca;Fil: Fanning, A.. No especifíca;Fil: Leaky, N.A.B.. No especifíca;Fil: Knowles, C.H.. No especifíca;Fil: Lee, K.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino UnidoFil: Shanahan, F.. University College Cork; IrlandaFil: Nally, K.. University College Cork; IrlandaFil: McLean, P.G.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino UnidoFil: Di Sabatino, A.. Universita Degli Studi Di Pavia; ItaliaFil: MacDonald, T.T.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino UnidoWiley Blackwell Publishing, Inc2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/135376Docena, Guillermo H.; Rovedatti, L.; Kruidenier, L.; Fanning, A.; Leaky, N.A.B.; et al.; Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 162; 1; 10-2010; 108-1150009-91041365-2249CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2249.2010.04203.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2010.04203.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:12:54Zoai:ri.conicet.gov.ar:11336/135376instacron: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:34982025-09-10 13:12:54.459CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
title Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
spellingShingle Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
Docena, Guillermo H.
CROHN'S DISEASE
LAMINA PROPRIA MONONUCLEAR CELL
P38 INHIBITOR
TNF-Α
ULCERATIVE COLITIS
title_short Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
title_full Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
title_fullStr Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
title_full_unstemmed Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
title_sort Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease
dc.creator.none.fl_str_mv Docena, Guillermo H.
Rovedatti, L.
Kruidenier, L.
Fanning, A.
Leaky, N.A.B.
Knowles, C.H.
Lee, K.
Shanahan, F.
Nally, K.
McLean, P.G.
Di Sabatino, A.
MacDonald, T.T.
author Docena, Guillermo H.
author_facet Docena, Guillermo H.
Rovedatti, L.
Kruidenier, L.
Fanning, A.
Leaky, N.A.B.
Knowles, C.H.
Lee, K.
Shanahan, F.
Nally, K.
McLean, P.G.
Di Sabatino, A.
MacDonald, T.T.
author_role author
author2 Rovedatti, L.
Kruidenier, L.
Fanning, A.
Leaky, N.A.B.
Knowles, C.H.
Lee, K.
Shanahan, F.
Nally, K.
McLean, P.G.
Di Sabatino, A.
MacDonald, T.T.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CROHN'S DISEASE
LAMINA PROPRIA MONONUCLEAR CELL
P38 INHIBITOR
TNF-Α
ULCERATIVE COLITIS
topic CROHN'S DISEASE
LAMINA PROPRIA MONONUCLEAR CELL
P38 INHIBITOR
TNF-Α
ULCERATIVE COLITIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) characterized by chronic relapsing mucosal inflammation. Tumour necrosis factor (TNF)-α, a known agonist of the mitogen-activated protein kinase (MAPK) pathway, is a key cytokine in this process. We aimed first to determine whether p38 MAPK is activated in IBD inflamed mucosa, and then studied the effect of four different p38α inhibitory compounds on MAPK phosphorylation and secretion of proinflammatory cytokines by IBD lamina propria mononuclear cells (LPMCs) and organ culture biopsies. In vivo phospho-p38α and p38α expression was evaluated by immunoblotting on intestinal biopsies from inflamed areas of patients affected by Crohn's disease and ulcerative colitis, and from normal mucosa of sex- and age-matched control subjects. Both mucosal biopsies and isolated LPMCs were incubated with four different p38α selective inhibitory drugs. TNF-α, interleukin (IL)-1β and IL-6 were measured in the organ and cell culture supernatants by enzyme-linked immunosorbent assay. We found higher levels of phospho-p38α in the inflamed mucosa of IBD patients in comparison to controls. All the p38α inhibitory drugs inhibited p38α phosphorylation and secretion of TNF-α, IL-1β and IL-6 from IBD LPMCs and biopsies. Activated p38α MAPK is up-regulated in the inflamed mucosa of patients with IBD. Additionally, all the p38α selective inhibitory drugs significantly down-regulated the activation of the MAPK pathway and the secretion of proinflammatory cytokines.
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: Rovedatti, L.. Universita Degli Studi Di Pavia; Italia
Fil: Kruidenier, L.. No especifíca;
Fil: Fanning, A.. No especifíca;
Fil: Leaky, N.A.B.. No especifíca;
Fil: Knowles, C.H.. No especifíca;
Fil: Lee, K.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
Fil: Shanahan, F.. University College Cork; Irlanda
Fil: Nally, K.. University College Cork; Irlanda
Fil: McLean, P.G.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
Fil: Di Sabatino, A.. Universita Degli Studi Di Pavia; Italia
Fil: MacDonald, T.T.. Immuno-Inflammation Centre of Excellence in Drug Discovery; Reino Unido
description Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) characterized by chronic relapsing mucosal inflammation. Tumour necrosis factor (TNF)-α, a known agonist of the mitogen-activated protein kinase (MAPK) pathway, is a key cytokine in this process. We aimed first to determine whether p38 MAPK is activated in IBD inflamed mucosa, and then studied the effect of four different p38α inhibitory compounds on MAPK phosphorylation and secretion of proinflammatory cytokines by IBD lamina propria mononuclear cells (LPMCs) and organ culture biopsies. In vivo phospho-p38α and p38α expression was evaluated by immunoblotting on intestinal biopsies from inflamed areas of patients affected by Crohn's disease and ulcerative colitis, and from normal mucosa of sex- and age-matched control subjects. Both mucosal biopsies and isolated LPMCs were incubated with four different p38α selective inhibitory drugs. TNF-α, interleukin (IL)-1β and IL-6 were measured in the organ and cell culture supernatants by enzyme-linked immunosorbent assay. We found higher levels of phospho-p38α in the inflamed mucosa of IBD patients in comparison to controls. All the p38α inhibitory drugs inhibited p38α phosphorylation and secretion of TNF-α, IL-1β and IL-6 from IBD LPMCs and biopsies. Activated p38α MAPK is up-regulated in the inflamed mucosa of patients with IBD. Additionally, all the p38α selective inhibitory drugs significantly down-regulated the activation of the MAPK pathway and the secretion of proinflammatory cytokines.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/135376
Docena, Guillermo H.; Rovedatti, L.; Kruidenier, L.; Fanning, A.; Leaky, N.A.B.; et al.; Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 162; 1; 10-2010; 108-115
0009-9104
1365-2249
CONICET Digital
CONICET
url http://hdl.handle.net/11336/135376
identifier_str_mv Docena, Guillermo H.; Rovedatti, L.; Kruidenier, L.; Fanning, A.; Leaky, N.A.B.; et al.; Down-regulation of p38 mitogen-activated protein kinase activation and proinflammatory cytokine production by mitogen-activated protein kinase inhibitors in inflammatory bowel disease; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 162; 1; 10-2010; 108-115
0009-9104
1365-2249
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2249.2010.04203.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2249.2010.04203.x
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/msword
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, 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
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score 12.993085

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