TY - JOUR
T1 - Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury
AU - Bhatia, Madhav
AU - Slavin, John
AU - Cao, Yuqing
AU - Basbaum, Allan I.
AU - Neoptolemos, John P.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
KW - Caerulein
KW - Multiple organ dysfunction syndrome
KW - Neurogenic inflammation
KW - Substance P
KW - Systemic inflammatory response syndrome
UR - http://www.scopus.com/inward/record.url?scp=0037403927&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00140.2002
DO - 10.1152/ajpgi.00140.2002
M3 - Article
C2 - 12684214
AN - SCOPUS:0037403927
SN - 0193-1857
VL - 284
SP - G830-G836
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 5 47-5
ER -