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

Abel D. Ang, Jack Rivers-Auty, Akhil Hegde, Isao Ishii, Madhav Bhatia

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 caeruleininduced 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 caeruleininduced pancreatitis, and its genetic deletion affords significant protection against acute pancreatitis and associated lung injury.

Original languageEnglish
Pages (from-to)G712-G721
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume305
Issue number10
DOIs
Publication statusPublished - 2013 Nov 15

Keywords

  • Cystathionine-γ-lyase
  • Hydrogen sulfide
  • Inflammation
  • Knockout
  • Pancreatitis

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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