Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury.
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.
Bhatia
Madhav
M
Department of Pharmacology, National University of Singapore, Singapore 117597. mbhatia@nus.edu.sg
Slavin
John
J
Cao
Yuqing
Y
Basbaum
Allan I
AI
Neoptolemos
John P
JP
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics* / Q000378:metabolism*
D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D002108:Ceruletide; D000681:Amylases