Pancreatitis-associated protein-I mRNA expression in mouse pancreas is upregulated by lipopolysaccharide independent of cerulein-pancreatitis

Background and Aims: It is well known that endotoxemia, which is caused by a bacterial infection, can exacerbate acute pancreatitis, whereas pancreati tis-associated protein (PAP) has the ability to induce bacterial aggregatio n. Pancreatitis-associated protein is supposed to protect the tissue from i nfection during inflammation. In order to clarify the relationship between PAP mRNA expression and endotoxemia during acute pancreatitis, the kinetic patterns of PAP-I mRNA in mouse pancreas treated with either cerulein or li popolysaccharide (LPS) or both were investigated in this study. Methods and Results: The administration of LPS (5 mg/kg) intraperitoneally resulted in a dramatic upregulation of PAP-I mRNA expression, increasing 18 .61-fold to a maximum at 12 h, then decreasing, but still sustaining at a h igh level and reaching baseline on day five. These changes were accompanied by the upregulation of tumor necrosis factor (TNF)-alpha, interleukin-1 be ta (IL-1 beta), interleukin 6 (IL-6) and interferon gamma (IFN gamma) mRNA expressions in the pancreas, but not by marked alterations of serum amylase , lactic dehydrogenase (LDH) and histology. Cerulein also increased PAP-I m RNA expression. However, the combination of cerulein and LPS was not able t o enhance PAP-I mRNA expression further, although more prominent pancreatit is based on significant changes of serum amylase, LDH and histology were ob served. Conclusion: These results suggest that PAP I mRNA might be modulated by end otoxemia, independent of cerulein-pancreatitis. There were no strong correl ations between PAP-I mRNA expression and the severity of pancreatitis. (C) 2001 Blackwell Science Asia Pty Ltd.