IDENTIFICATION OF GENES DIFFERENTIALLY EXPRESSED IN A NOVEL MODEL OF ACUTE SEVERE NECROTIZING PANCREATITIS IN MICE

Abstract

The outcome in necrotizing pancreatitis is depending on the development and intensity of the systemic inflammatory response syndrome (SIRS). The mechanisms involved in the occurrence of SIRS are only understood in part. Our aim was to identify differentially expressed genes by microarray analysis in organs affected from SIRS induced by acute pancreatitis and map these genes to known pathways. In 8 animals, severe necrotizing pancreatitis was induced by retrograde infusion of 5% sodium taurocholate into the common bile duct in mice leading to 60% lethality from acute pancreatitis within 24 hours. 5 animals were sham operated controls receiving saline infusion in the common bile duct. 8 hours after induction of acute pancreatitis the animals were sacrificed and total RNA was isolated from liver, spleen, lungs and intestine. RNAs were pooled and Cy3 as wells as Cy5 labeled cDNA was prepared from 40 μg of pooled total RNA. Hybridization of PIQOR immunology mouse sense microarrays was performed overnight. Online pathway analysis was performed by pathway explorer utilizing Biocarta and KEGG pathways. The number of differentially expressed genes in liver (400; 37.38%) and spleen (408; 38.13%) was higher than observed in small intestine (163; 15.24%) and lung (154; 14.39%), thus indicating the involvement of these organs in the systemic changes induced by acute pancreatitis. Expression of 11 (1.02%) identical genes were altered in all 4 tissues, 44 (4.11%) in 3 and 291 (27.20%) in 2 tissues. In liver and spleen, altered genes mapped significantly to 14 and 8 pathways respectively (p < 0.05) including TNFR signaling pathway and oxidative stress induced gene expression pathway. Pathway analysis of intestine and lung only revealed 3 and 4 pathways with significant alterations. Our data provides first evidence of the involvement of several signaling pathways related to severe necrotizing pancreatitis in mice and builds the foundation for several hypotheses for immunologic alterations induced by necrotizing pancreatitis.