Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 14, 2006; 12(42): 6806-6811
Published online Nov 14, 2006. doi: 10.3748/wjg.v12.i42.6806
Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins
Emad Kandil, Yin-Yao Lin, Martin H Bluth, Hong Zhang, Gabriel Levi, Michael E Zenilman
Emad Kandil, Yin-Yao Lin, Martin H Bluth, Hong Zhang, Michael E Zenilman, Department of Surgery, State University of New York Downstate Medical Center, Brooklyn, New York, United States
Martin H Bluth, Gabriel Levi, Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, New York, United States
Author contributions: All authors contributed equally to the work.
Supported by the National Institutes of Health, No. DK054511
Correspondence to: Michael E Zenilman, MD, Department of Surgery, SUNY Downstate Medical Center, Box 40, 450 Clarkson Avenue, Brooklyn, NY 11203, United States. michael.zenilman@downstate.edu
Telephone: +1-718-2701421 Fax: +1-718-2702826
Received: May 2, 2006
Revised: September 15, 2006
Accepted: September 22, 2006
Published online: November 14, 2006
Abstract

AIM: To examine the influence of dexamethasone on pancreatitis-associated protein (PAP) gene expression using both in vitro and in vivo models of acute pancreatitis and to study how PAP gene expression correlates with severity of pancreatitis.

METHODS: In vitro, IL-6 stimulated pancreas acinar AR42J cells were cultured with increasing concentrations of dexamethasone and assayed for PAP expression (RT-PCR). In vivo, pancreatitis was induced in rats by retrograde injection of 40 g/L taurocholate into the pancreatic duct. Animals were pretreated with dexamethasone (2 mg/kg) daily or saline for 4 d. Pancreata and serum were harvested after 24 h and gene expression levels of PAPI, II and III were measured by RT-PCR. Severity of pancreatitis was based on serum amylase, pancreatic wet weight, and histopathological score.

RESULTS: In vitro, dexamethasone and IL-6 induced a marked transcription of PAPI, II and III genes in AR42J cells at 24 h (P < 0.05 for all comparisons). In vivo, pancreas mRNA levels of PAPI, II or III increased by 2.6-fold, 1.9-fold, and 1.3-fold respectively after dexamethasone treatment, compared with saline treated animals. Serum amylase levels and edema were significantly lower in the dexamethasone group compared with the saline group. Histopathologic evaluation revealed less inflammation and necrosis in pancreata obtained from dexamethasone treated animals (P < 0.05).

CONCLUSION: Dexamethasone significantly decreases the severity of pancreatitis. The protective mechanism of dexamethasone may be via upregulating PAP gene expression during injury.

Keywords: Pancreatitis; Pancreatitis-associated protein; Pancreatitis-associated protein; Dexamethasone