The ER chaperone GRP78 is associated with the severity of cerulein-induced pancreatic inflammation via regulating apoptosis of pancreatic acinar cells.
OBJECTIVE
To study the potential role of the 78kDa glucose regulated protein (GRP78) in the pathogenesis of acute pancreatitis (AP) in vitro.


METHODS
AR42J cells were stimulated by cerulein or cerulein plus lipoplysaccharide (LPS). The severity of pancreatic inflammation was evaluated by amylase, lipase, TNF-a, and IL-6. Apoptosis was determined by flow cytometry; the expressions of apoptotic genes, GRP78 and the downstream molecules were determined by real-time quantitative PCR and Western blot.


RESULTS
After cerulein stimulation, the levels of amylase, lipase, TNF-a and IL-6 were all increased, with a more pronounced increase after cerulein plus LPS stimulation. Apoptosis was different in two cell models, high apoptosis in cerulein group; whereas cerulein plus LPS induced relatively less apoptosis. Apoptotic gene expressions revealed more pronounced increase in the cerulein group than those in cerulein plus LPS group. The expressions of GRP78 and downstream molecules were different in two cell models. GRP78 expression was down-regulated in cerulein group and upregulated in cerulein plus LPS group.


CONCLUSIONS
GRP78 expression was associated with apoptosis and the severity of cerulein-induced pancreatic inflammation, indicating that GRP78 might prevent apoptosis in pancreatic acinar cells thereby deteriorating the severity of AP.
Department of Gastroenterological Surgery, Sichuan University, Sichuan Province, China.
Yong
Y
Liu
Zong-Guang
ZG
Zhou
Ke-Ling
KL
Chen
Bing
B
Zhou
Lie
L
Yang
Hui
H
Yan
Yuan
Y
Li
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D002108:Ceruletide / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009336:Necrosis; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D000071701:Regulatory Factor X Transcription Factors; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
D000681:Amylases; D002108:Ceruletide; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D008049:Lipase; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP