Nakagawa A, Nagino M. 15-Deoxy-⌬ 12,14 -prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis. Am J Physiol Gastrointest Liver Physiol 298: G410 -G418, 2010. First published January 7, 2010 doi:10.1152/ajpgi.00233.2009.-Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-␥ (PPAR␥), such as 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15D-PGJ2), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ2 treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (ShamϩSaline), sham operation with intraperitoneal LPS infusion (ShamϩLPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDLϩSaline), and BDL with LPS infusion into the bile duct (BDLϩLPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the ShamϩLPS and the BDLϩLPS group were divided into two groups (with and without 15D-PGJ2 treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDLϩLPS group compared with those in the BDLϩSaline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ2 significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ2 in the BDLϩLPS group. These results clearly demonstrate that 15D-PGJ2 inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.bile duct ligation; hyaluronic acid clearance; NF-B; portal venous pressure ACUTE OBSTRUCTIVE CHOLANGITIS (AOC) due to infections in the biliary tract is a common occurrence in the clinical setting. Despite recent advances in the treatment of infectious diseases, AOC remains a significant cause of morbidity and mortality. One of the leading reasons for AOC-related death is acute liver failure, which can be triggered by an excessive inflammatory response in the liver. However, the precise mechanism of AOC-induced acute liver failure remains unclear.A number of reports have focused on the role of proinflammatory cytokines, such as tumor necrosis factor-␣ (TNF-␣) and interleukin-6 (IL-6), in the pathophysiology of organ injury from AOC (14). Increases in the levels of these proinflammatory cytokines have been shown to correlate strongly with the severity of multiple organ failure and with the mortality from AOC (12). Ex...