OBJECTIVES: Abdominal sepsis is a common, life-threatening condition in critically ill patients, and pseudomonas peritonitis remains a serious clinical complication of peritoneal dialysis. This study was performed to determine whether peritonitis induces lung damage through the c-Jun NH2-terminal kinase. DESIGN: : Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Peritonitis models in the mice. INTERVENTIONS: Wild-type, c-Jun NH2-terminal kinase1, and c-Jun NH2-terminal kinase1 mice were subjected to peritonitis. A c-Jun NH2-terminal kinase inhibitor, SP600125 or leflunomide, was administered to mice immediately after peritonitis. MEASUREMENTS AND MAIN RESULTS: The changes of plasma dihydrorhodamine 123 oxidation level, the myeloperoxidase activity, and extravasations of Evans blue dye of lung in wild-type mice with or without c-Jun NH2-terminal kinase inhibitor; c-Jun NH2-terminal kinase1 mice and c-Jun NH2-terminal kinase1 mice; and chimeric mice (wild-type --> wild-type, c-Jun NH2-terminal kinase1 --> wild-type) with Pseudomonas aeruginosa-induced peritonitis were determined to evaluate the role of c-Jun NH2-terminal kinase signaling of the hematopoietic cells in peritonitis-induced lung damage. Our results showed that peritonitis induced dihydrorhodamine 123 oxidation, myeloperoxidase activity, activator protein-1 (AP-1) DNA binding activity, phosphorylated-c-Jun NH2-terminal kinase and inducible nitric oxide synthase expression, and Evans blue dye extravasations in lungs, and administration of specific c-Jun NH2-terminal kinase inhibitor decreased the peritonitis-induced dihydrorhodamine 123 oxidation and lung damage. Also, both c-Jun NH2-terminal kinase1 and c-Jun NH2-terminal kinase1 mice showed a decreased dihydrorhodamine 123 oxidation and lung damage after peritonitis. Finally, dihydrorhodamine 123 oxidation, reactive oxygen species, inducible nitric oxide synthase expression, and lung damage were decreased in c-Jun NH2-terminal kinase1 --> wild-type but not in wild-type --> c-Jun NH2-terminal kinase1 chimeric mice. CONCLUSIONS: Collectively, our data suggest that peritonitis-induced inducible nitric oxide synthase expression, peroxynitrite production, and lung damage depend on the c-Jun NH2-terminal kinase signaling of the hematopoietic cells.
OBJECTIVES:Abdominal sepsis is a common, life-threatening condition in critically ill patients, and pseudomonas peritonitis remains a serious clinical complication of peritoneal dialysis. This study was performed to determine whether peritonitis induces lung damage through the c-Jun NH2-terminal kinase. DESIGN: : Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Peritonitis models in the mice. INTERVENTIONS: Wild-type, c-Jun NH2-terminal kinase1, and c-Jun NH2-terminal kinase1 mice were subjected to peritonitis. A c-Jun NH2-terminal kinase inhibitor, SP600125 or leflunomide, was administered to mice immediately after peritonitis. MEASUREMENTS AND MAIN RESULTS: The changes of plasma dihydrorhodamine 123 oxidation level, the myeloperoxidase activity, and extravasations of Evans blue dye of lung in wild-type mice with or without c-Jun NH2-terminal kinase inhibitor; c-Jun NH2-terminal kinase1 mice and c-Jun NH2-terminal kinase1 mice; and chimeric mice (wild-type --> wild-type, c-Jun NH2-terminal kinase1 --> wild-type) with Pseudomonas aeruginosa-induced peritonitis were determined to evaluate the role of c-Jun NH2-terminal kinase signaling of the hematopoietic cells in peritonitis-induced lung damage. Our results showed that peritonitis induced dihydrorhodamine 123 oxidation, myeloperoxidase activity, activator protein-1 (AP-1) DNA binding activity, phosphorylated-c-Jun NH2-terminal kinase and inducible nitric oxide synthase expression, and Evans blue dye extravasations in lungs, and administration of specific c-Jun NH2-terminal kinase inhibitor decreased the peritonitis-induced dihydrorhodamine 123 oxidation and lung damage. Also, both c-Jun NH2-terminal kinase1 and c-Jun NH2-terminal kinase1 mice showed a decreased dihydrorhodamine 123 oxidation and lung damage after peritonitis. Finally, dihydrorhodamine 123 oxidation, reactive oxygen species, inducible nitric oxide synthase expression, and lung damage were decreased in c-Jun NH2-terminal kinase1 --> wild-type but not in wild-type --> c-Jun NH2-terminal kinase1 chimeric mice. CONCLUSIONS: Collectively, our data suggest that peritonitis-induced inducible nitric oxide synthase expression, peroxynitrite production, and lung damage depend on the c-Jun NH2-terminal kinase signaling of the hematopoietic cells.
Authors: Ashley R Kochanek; Eugene Y Fukudome; Yongqing Li; Eleanor J Smith; Baoling Liu; George C Velmahos; Marc deMoya; David King; Hasan B Alam Journal: J Surg Res Date: 2011-07-05 Impact factor: 2.192