| First Author | Ang AD | Year | 2013 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 305 |
| Issue | 10 | Pages | G712-21 |
| PubMed ID | 24008358 | Mgi Jnum | J:210565 |
| Mgi Id | MGI:5571447 | Doi | 10.1152/ajpgi.00044.2013 |
| Citation | Ang AD, et al. (2013) The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse. Am J Physiol Gastrointest Liver Physiol 305(10):G712-21 |
| abstractText | 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. |
