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.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
authors.forename: Violeta
authors.initials: V
authors.lastname: García-Hernández
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
authors.forename: Nancy
authors.initials: N
authors.lastname: Sarmiento
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Bernal
authors.affiliation: Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Hernández-Hernández
authors.affiliation: Department of Physiology and Pharmacology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Calvo
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain. Electronic address: sanyaj@usal.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez-Yagüe
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; C070693:Scarb2 protein, rat; D002108:Ceruletide; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D020889:Rolipram
keywords: Cerulein; Experimental acute pancreatitis; Infiltration inhibition; LIMP-2; MAPK inhibition