November 12, 2014
Notes: Andersson, Bodil
Scand J Gastroenterol. 2013 Dec;48(12):1459-65. doi: 10.3109/00365521.2013.843201. Epub 2013 Oct 16.
Author Address: Departments of Surgery, Clinical science in Lund, Lund University and Skane University hospital , Lund , Sweden.
Reference Type: Journal Article
Record Number: 4977Author: Ang, A. D., Rivers-Auty, J., Hegde, A., Ishii, I. and Bhatia, M.
Title: The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse
Journal: Am J Physiol Gastrointest Liver Physiol
Date: Nov 15
Short Title: The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse
Alternate Journal: American journal of physiology. Gastrointestinal and liver physiology
ISSN: 1522-1547 (Electronic)
Accession Number: 24008358
Gene Expression Regulation/physiology
Lung Diseases/chemically induced/metabolism
Mice, Inbred C57BL
Protein Kinase C/genetics/metabolism
Abstract: Hydrogen sulfide (H2S) has been reported to be involved in the signaling of the inflammatory response; however, there are differing views as to whether it is pro- or anti-inflammatory. In this study, we sought to determine whether endogenously synthesized H2S via cystathionine-gamma-lyase (CSE) plays a pro- or anti-inflammatory role in caerulein-induced pancreatitis. To investigate this, we used mice genetically deficient in CSE to elucidate the function of CSE in caerulein-induced acute pancreatitis. We compared the inflammatory response and tissue damage of wild-type (WT) and CSE knockout (KO) mice following 10 hourly administrations of 50 mug/kg caerulein or saline control. From this, we found that the CSE KO mice showed significantly less local pancreatic damage as well as acute pancreatitis-associated lung injury compared with the WT mice. There were also lower levels of pancreatic eicosanoid and cytokines, as well as reduced acinar cell NF-kappaB activation in the CSE KO mice compared with WT mice. Additionally, in WT mice, there was a greater level of pancreatic CSE expression and sulfide-synthesizing activity in caerulein-induced pancreatitis compared with the saline control. When comparing the two saline-treated control groups, we noted that the CSE KO mice showed significantly less pancreatic H2S-synthesizing activity relative to the WT mice. These results indicate that endogenous H2S generated by CSE plays a key proinflammatory role via NF-kappaB activation in caerulein-induced pancreatitis, and its genetic deletion affords significant protection against acute pancreatitis and associated lung injury.