Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen-derived free radicals have been implicated in the pathogenesis of acute pancreatitis, yet adaptive responses in the pancreas in vivo to oxidative stress remain poorly defined. We have investigated expression of the stress protein heme oxygenase in the intact pancreas of rats with caerulein-induced pancreatitis and in cultured pancreatic acinar and islet cell lines. Expression of inducible heme oxygenase-1 (HO-1) in the pancreas in vivo was enhanced 12-24 h after induction of pancreatitis. In murine islet (betaTC3) and rat acinar (AR42J) pancreatic cells, H2O2, methyl viologen, cadmium chloride and diethylmaleate enhanced HO-1 expression in a dose- and time-dependent manner, without altering expression of constitutive HO-2. Enhanced expression of HO-1 in the pancreas in vivo and pancreatic islet and acinar cells may contribute to cellular defences against oxidative stress associated with acute pancreatitis.
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PMID:Expression of stress proteins heme oxygenase-1 and -2 in acute pancreatitis and pancreatic islet betaTC3 and acinar AR42J cells. 908 94

Hemin upregulates heme oxygenase-1 (HO-1), a stress-induced enzyme implicated in protection from a variety of injuries while its related isoform HO-2 is constitutively expressed. The role of hemin or HO-1 in the pancreas and their potential modulation of pancreatic injury are unknown. We show that HO-1 is induced in pancreatitis caused by caerulein and more prominently in severe pancreatitis caused by feeding a choline-deficient diet (CDD). Intraperitoneal hemin administration dramatically increases peritoneal and pancreas macrophages that overexpress HO-1 in association with pancreatic induction of the chemoattractants monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha but not RANTES or macrophage inflammatory protein-2. Hemin administration before CDD feeding protected 8 of 8 mice from lethality while 7 of 16 controls died. Protection is mediated by HO-1-overexpressing macrophages since hemin-primed macrophages home to the pancreas after transfer to naive mice and protect from CDD-induced pancreatitis. Suppression of hemin-primed peritoneal cell HO-1 using HO-1-specific small interfering RNA prior to cell transfer abolishes protection from CDD-induced pancreatitis. Similarly, hemin pretreatment in caerulein-induced pancreatitis reduces serum amylase and lipase, decreases pancreatic trypsin generation, and protects from lung injury. Therefore, hemin-like compounds or hemin-activated macrophages may offer novel therapeutic approaches for preventing acute pancreatitis and its pulmonary complication via upregulation of HO-1.
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PMID:Hemin-activated macrophages home to the pancreas and protect from acute pancreatitis via heme oxygenase-1 induction. 1623 66