O016 Leukocyte gene expression profiles in fatty acid ethyl ester-induced acute pancreatitis

Abstract Introduction Gene expression has been poorly studied in acute pancreatitis (AP). We examined leukocyte differential gene expression (DGE) in fatty acid ethyl ester-induced AP (FAEE-AP), which models alcohol-associated AP. Methods Wild type C57Bl/7 mice were randomly divided into 5 groups of 6 receiving two hourly intraperitoneal injections of either 150 mg/kg palmitoleic acid (POA) and 1.35 g/kg ethanol (FAEE-AP), or 50 mg/kg POA and 1.35 g/kg ethanol (FAEE-AP), or 1.35 g/kg ethanol alone (contrast), or saline (control), or no injections (control). Mice were humanely killed at 12 hours for AP assessment and Agilent two-colour RNA blood microarray, with Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses (DGE P <0.05, log FC >1). Results AP developed in FAEE-AP, more severe with 150 mg/kg POA, but not in either control group, with <10 DGEs between the FAEE-AP groups, and between saline and no injection groups. Comparison between combined FAEE and combined controls identified 1180 upregulated and 355 downregulated mRNAs. GO and KEGG analyses found DGEs strongly enriched in inflammatory response and NOD-like receptor signalling pathways, respectively. Comparison of ethanol alone and controls identified 307 upregulated and 82 downregulated mRNAs, enriched in mononuclear cell differentiation and cytokine-cytokine receptor interaction; 336 of 389 DGEs overlapped with FAEE-AP. Conclusion These data suggest appropriateness of either control, with little detectable difference in DGEs between FAEE-AP protocols despite differing AP severity; limited additional data were obtained using an ethanol group. Comparison with other AP models may improve understanding of disease mechanisms.