Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

2003 ◽  
Vol 284 (5) ◽  
pp. G830-G836 ◽  
Author(s):  
Madhav Bhatia ◽  
John Slavin ◽  
Yuqing Cao ◽  
Allan I. Basbaum ◽  
John P. Neoptolemos
Keyword(s):  
Acute Pancreatitis ◽  
Substance P ◽  
Lung Injury ◽  
Gene Deletion ◽  
Gene Products ◽  
Nk1 Receptors ◽  
Proinflammatory Mediators ◽  
Pancreatic Damage ◽  
Impaired Lung Function ◽  
Nk2 Receptor

Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.

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

2013 ◽  
Vol 305 (10) ◽  
pp. G712-G721 ◽  
Author(s):  
Abel D. Ang ◽  
Jack Rivers-Auty ◽  
Akhil Hegde ◽  
Isao Ishii ◽  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Saline Control ◽  
Wild Type ◽  
Control Groups ◽  
Pancreatic Damage ◽  
Genetic Deletion ◽  
Anti Inflammatory ◽  
Proinflammatory Role

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.

scholarly journals Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

1998 ◽  
Vol 95 (8) ◽  
pp. 4760-4765 ◽  
Author(s):  
M. Bhatia ◽  
A. K. Saluja ◽  
B. Hofbauer ◽  
J.-L. Frossard ◽  
H. S. Lee ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Substance P ◽  
Lung Injury ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Protective effects of coumestrol on lipopolysaccharide-induced acute lung injury via the inhibition of proinflammatory mediators and NF-κB activation

2017 ◽  
Vol 34 ◽  
pp. 181-188 ◽  
Author(s):  
Heung Joo Yuk ◽  
Jae Won Lee ◽  
Hyun Ah Park ◽  
Ok-Kyoung Kwon ◽  
Kyeong-Hwa Seo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effects ◽  
Proinflammatory Mediators
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