Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development

[EN]Lysosomal integral membrane protein-2 (LIMP-2) is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response. It is known that lysosomes play a central role in acute pancreatitis, with inflammatory cell infiltration triggering the disease...

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Autores: García Hernández, Violeta, Sarmiento, Nancy, Sánchez Bernal, María Carmen, Coveñas Rodríguez, Rafael, Hernández Hernández, Ángel, Calvo Andrés, José Julián, Sánchez Yagüe, Jesús
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/155151
Acceso en línea:http://hdl.handle.net/10366/155151
Access Level:acceso embargado
Palabra clave:LIMP-2
Infiltration inhibition
MAPK inhibition
Cerulein
Experimental acute pancreatitis
Mitogen-Activated Protein Kinases
Rats
Ceruletide
Animals
Rolipram
Gene Expression Regulation
Signal Transduction
Neutrophil Infiltration
Pancreatitis
Cyclic AMP
regulación de la expresión génica
transducción de señales
animales
infiltración de neutrófilos
pancreatitis
rolipram
proteína cinasas activadas por mitógenos
ratas
ceruletida
AMP cíclico
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spelling Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its developmentGarcía Hernández, VioletaSarmiento, NancySánchez Bernal, María CarmenCoveñas Rodríguez, RafaelHernández Hernández, ÁngelCalvo Andrés, José JuliánSánchez Yagüe, JesúsLIMP-2Infiltration inhibitionMAPK inhibitionCeruleinExperimental acute pancreatitisMitogen-Activated Protein KinasesRatsCeruletideAnimalsRolipramGene Expression RegulationSignal TransductionNeutrophil InfiltrationPancreatitisCyclic AMPregulación de la expresión génicatransducción de señalesanimalesinfiltración de neutrófilospancreatitisrolipramproteína cinasas activadas por mitógenosratasceruletidaAMP cíclico[EN]Lysosomal integral membrane protein-2 (LIMP-2) is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response. It is known that lysosomes play a central role in acute pancreatitis, with inflammatory cell infiltration triggering the disease early on. In this study we report increases in pancreatic LIMP-2 protein and mRNA levels as early events that occur during the development of cerulein (Cer)-induced acute pancreatitis (AP) in rats. GdCl3, a macrophage inhibitor, but not FK506, a T lymphocyte inhibitor, was able to reverse the increase in LIMP-2 expression after Cer treatment, although such reversion was abolished if the animals were depleted of neutrophils due to a vinblastine sulfate pre-treatment. Immunostaining revealed that the cellular source of LIMP-2 was mainly acinar cells. Additionally, pre-treatments with the MAPKs inhibitors SP600125 and PD98059, inhibitors of JNK and ERK½ activation, respectively, but not of rolipram, a type IV phosphodiesterase inhibitor, suppressed the increase in the expression of LIMP-2 after Cer administration. Together, these results indicate that neutrophils are able to drive a macrophage activation that would regulate the increase in LIMP-2 expression during the early phase of Cer-induced AP, with the stress kinases JNK and ERK½ also playing a coordinated role in the increase of LIMP-2 expression due to Cer.Elsevierinfo202420242016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/155151reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)Inglésinfo:eu-repo/semantics/embargoedAccessoai:gredos.usal.es:10366/1551512026-06-07T06:28:51Z
dc.title.none.fl_str_mv Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
title Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
spellingShingle Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
García Hernández, Violeta
LIMP-2
Infiltration inhibition
MAPK inhibition
Cerulein
Experimental acute pancreatitis
Mitogen-Activated Protein Kinases
Rats
Ceruletide
Animals
Rolipram
Gene Expression Regulation
Signal Transduction
Neutrophil Infiltration
Pancreatitis
Cyclic AMP
regulación de la expresión génica
transducción de señales
animales
infiltración de neutrófilos
pancreatitis
rolipram
proteína cinasas activadas por mitógenos
ratas
ceruletida
AMP cíclico
title_short Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
title_full Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
title_fullStr Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
title_full_unstemmed Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
title_sort Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development
dc.creator.none.fl_str_mv García Hernández, Violeta
Sarmiento, Nancy
Sánchez Bernal, María Carmen
Coveñas Rodríguez, Rafael
Hernández Hernández, Ángel
Calvo Andrés, José Julián
Sánchez Yagüe, Jesús
author García Hernández, Violeta
author_facet García Hernández, Violeta
Sarmiento, Nancy
Sánchez Bernal, María Carmen
Coveñas Rodríguez, Rafael
Hernández Hernández, Ángel
Calvo Andrés, José Julián
Sánchez Yagüe, Jesús
author_role author
author2 Sarmiento, Nancy
Sánchez Bernal, María Carmen
Coveñas Rodríguez, Rafael
Hernández Hernández, Ángel
Calvo Andrés, José Julián
Sánchez Yagüe, Jesús
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv LIMP-2
Infiltration inhibition
MAPK inhibition
Cerulein
Experimental acute pancreatitis
Mitogen-Activated Protein Kinases
Rats
Ceruletide
Animals
Rolipram
Gene Expression Regulation
Signal Transduction
Neutrophil Infiltration
Pancreatitis
Cyclic AMP
regulación de la expresión génica
transducción de señales
animales
infiltración de neutrófilos
pancreatitis
rolipram
proteína cinasas activadas por mitógenos
ratas
ceruletida
AMP cíclico
topic LIMP-2
Infiltration inhibition
MAPK inhibition
Cerulein
Experimental acute pancreatitis
Mitogen-Activated Protein Kinases
Rats
Ceruletide
Animals
Rolipram
Gene Expression Regulation
Signal Transduction
Neutrophil Infiltration
Pancreatitis
Cyclic AMP
regulación de la expresión génica
transducción de señales
animales
infiltración de neutrófilos
pancreatitis
rolipram
proteína cinasas activadas por mitógenos
ratas
ceruletida
AMP cíclico
description [EN]Lysosomal integral membrane protein-2 (LIMP-2) is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response. It is known that lysosomes play a central role in acute pancreatitis, with inflammatory cell infiltration triggering the disease early on. In this study we report increases in pancreatic LIMP-2 protein and mRNA levels as early events that occur during the development of cerulein (Cer)-induced acute pancreatitis (AP) in rats. GdCl3, a macrophage inhibitor, but not FK506, a T lymphocyte inhibitor, was able to reverse the increase in LIMP-2 expression after Cer treatment, although such reversion was abolished if the animals were depleted of neutrophils due to a vinblastine sulfate pre-treatment. Immunostaining revealed that the cellular source of LIMP-2 was mainly acinar cells. Additionally, pre-treatments with the MAPKs inhibitors SP600125 and PD98059, inhibitors of JNK and ERK½ activation, respectively, but not of rolipram, a type IV phosphodiesterase inhibitor, suppressed the increase in the expression of LIMP-2 after Cer administration. Together, these results indicate that neutrophils are able to drive a macrophage activation that would regulate the increase in LIMP-2 expression during the early phase of Cer-induced AP, with the stress kinases JNK and ERK½ also playing a coordinated role in the increase of LIMP-2 expression due to Cer.
publishDate 2016
dc.date.none.fl_str_mv 2016
2024
2024
info
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/155151
url http://hdl.handle.net/10366/155151
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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