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Int J Biochem Cell Biol. 2016 Mar;72:109-117. doi: 10.1016/j.biocel.2016.01.010. Epub 2016 Jan 18.

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.

Author information

1
Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
2
Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Spain.
3
Department of Physiology and Pharmacology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain.
4
Department of Biochemistry and Molecular Biology, University of Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca), Spain. Electronic address: sanyaj@usal.es.

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.

KEYWORDS:

Cerulein; Experimental acute pancreatitis; Infiltration inhibition; LIMP-2; MAPK inhibition

PMID:
26794464
DOI:
10.1016/j.biocel.2016.01.010
[Indexed for MEDLINE]

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