title: Role of p38 mitogen-activated protein kinase pathway on renal failure in the infant rat after burn injury.
abstract: The p38 mitogen-activated protein kinase (MAPK) pathway is a proinflammatory signal transduction pathway for the production of cytokines and cellular response to stress, such as bacterial LPS or ischemia. We examined the effects of FR167653, a specific inhibitor of p38 MAPK, to explore the relationship between intestinal barrier damage and remote renal dysfunction. Immunohistochemical data showed the accumulation of neutrophils in the intestine after burn, and a horseradish peroxidase (HRP) tracer experiment showed burn-induced intestinal barrier damage. Our quantitative bacterial culture data demonstrated that viable bacteria reached the remote organs after burn and prevented the invading viable bacteria from using FR167653. Western blotting identified increased phosphorylation of p38 MAPK in the kidney after burn, and it may also have shown the possibility that endotoxin associated with the bacterial translocation enhances the activation of the p38 MAPK pathway. We blocked the intestinal barrier damage using FR167653, which resulted in reduced neutrophils in the intestine. FR167653 also prevented the increased phosphorylation of p38 MAPK in the kidney, which resulted in reduced neutrophils in the glomerulus and the reduction of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta mRNA in the kidneys, and, finally, prevented burn-induced renal failure. This study provides evidence for the hypothesis that the p38 MAPK pathway controls inflammatory mediators and not only improves intestinal function but also reduces remote renal failure after burn. We identified the pathophysiologic role of the p38 MAPK pathway in the development of renal failure after burn.
authors.affiliation: Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. kita@med.uoeh-u.ac.jp
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kasai
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018988:Bacterial Translocation; D002056:Burns / Q000150:complications* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000293:injuries; D007583:Jejunum / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases