Rolipram and SP600125 suppress the early increase in PTP1B expression during cerulein-induced pancreatitis in rats.

Abstract:

OBJECTIVES:To analyze the expression modulation of pancreatic protein tyrosine phosphatase (PTP)1B during the development of cerulein (Cer)-induced acute pancreatitis (AP) and the effect of inhibition of type 4 phosphodiesterase and c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 on its expression levels. METHODS:Acute pancreatitis was induced in rats by subcutaneous injections of 20 microg Cer per kilogram body weight at hourly intervals, and the animals were killed at 2, 4, or 9 hours after the first injection. Neutropenia was induced with vinblastine sulfate. Phosphodiesterase and the mitogen-activated protein kinases were inhibited with rolipram and SP600125, respectively, before the induction of AP. RESULTS:Protein tyrosine phosphatase 1B increases its expression at the levels of both protein and messenger RNA during the early phase of Cer-induced AP. The increase in protein expression persisted along the development of the disease, and neutrophil infiltration seemed to play a central role. Rolipram and SP600125 pretreatments mostly suppressed the increase in the expression of PTP1B during the early phase of AP. CONCLUSIONS:Cerulein-induced AP is associated with an increase in the expression of PTP1B in its early phase. An increase in cyclic adenosine monophosphate levels in inflammatory cells and the inhibition of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 are able to suppress the increase in PTP1B protein level.

journal_name

Pancreas

journal_title

Pancreas

authors

Sarmiento N,Sánchez-Bernal C,Pérez N,Sardina JL,Mangas A,Calvo JJ,Sánchez-Yagüe J

doi

10.1097/MPA.0b013e3181c314b3

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

639-45

issue

5

eissn

0885-3177

issn

1536-4828

journal_volume

39

pub_type

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