The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse.

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-γ-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 μg/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-κB 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-κB activation in caerulein-induced pancreatitis, and its genetic deletion affords significant protection against acute pancreatitis and associated lung injury.

• Authors: Abel D Ang, Jack Rivers-Auty, Akhil Hegde, Isao Ishii, Madhav Bhatia
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 305 Issue 10 Pg. G712-21 (Nov 15 2013) ISSN: 1522-1547 [Electronic] United States
• PMID: 24008358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Ceruletide
• Protein Kinase C
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Ceruletide (toxicity)
• Cystathionine gamma-Lyase (genetics, metabolism)
• Gene Expression Regulation (physiology)
• Hydrogen Sulfide (metabolism)
• Lung Diseases (chemically induced, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B (genetics, metabolism)
• Pancreatitis (chemically induced, genetics, metabolism)
• Protein Kinase C (genetics, metabolism)