Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins.
OBJECTIVE
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 PAP I, 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 PAP I, II and III genes in AR42J cells at 24 h (P < 0.05 for all comparisons). In vivo, pancreas mRNA levels of PAP I, 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).


CONCLUSIONS
Dexamethasone significantly decreases the severity of pancreatitis. The protective mechanism of dexamethasone may be via upregulating PAP gene expression during injury.
Kandil
Emad
E
Department of Surgery, SUNY Downstate Medical Center, Box 40, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Lin
Yin-Yao
YY
Bluth
Martin-H
MH
Zhang
Hong
H
Levi
Gabriel
G
Zenilman
Michael-E
ME
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics; D003907:Dexamethasone / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D015854:Up-Regulation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002756:Cholagogues and Choleretics; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D013656:Taurocholic Acid; D003907:Dexamethasone