Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis.

Abstract

Blood leukocytes play a major role in mediating local and systemic inflammation during acute pancreatitis. We hypothesize that peripheral blood mononuclear cells (PBMCs) in circulation exhibit unique changes in gene expression and could provide a "reporter" function that reflects the inflammatory response in the pancreas with acute pancreatitis. To determine specific changes in blood leukocytes during acute pancreatitis, we studied the gene transcription profile in PBMCs in a rat model of experimental pancreatitis (sodium taurocholate). Normal rats, saline controls, and a model of septic shock were used as a controls. Complementary RNA obtained from PBMCs of each group (n = 3 in each group) were applied to Affymetrix rat genome DNA GeneChip arrays. Main Outcome Measure Changes in gene expression. From the 8799 rat genes analyzed, 140 genes showed unique significant changes in their expression in PBMCs during the acute phase of pancreatitis, but not in sepsis. Among the 140 genes, 57 were up-regulated, while 69 were down-regulated. Platelet-derived growth factor receptor, prostaglandin E(2) receptor, and phospholipase D(1) were among the top up-regulated genes. Others included genes involved in G protein-coupled receptor and transforming growth factor beta-mediated signaling pathways, while genes associated with apoptosis, glucocorticoid receptors, and even the cholecystokinin receptor were down-regulated. Microarray analysis in transcriptional profiling of PBMCs showed that genes that are uniquely related to molecular and pancreatic function display differential expression in acute pancreatitis. Profiling genes obtained from an easily accessible source during severe pancreatitis may identify surrogate markers for disease severity.