INDUCTION OF LITHOSTATHINE REG MESSENGER-RNA EXPRESSION BY SERUM FROMRATS WITH ACUTE-PANCREATITIS AND CYTOKINES IN PANCREATIC ACINAR AR-42J CELLS/

During the acute phase of pancreatitis, expression of most pancreatic enzymes decreases, whereas mRNAs of pancreatitis associated protein an d lithostathine/reg increase dramatically, In the present study we hav e investigated the effect of serum from rats with acute pancreatitis ( SAP) and cytokines on the lithostathine/reg mRNA expression in AR-42J cells, Lithostathine/reg mRNA was strongly induced by SAP in a dose-de pendent manner, Induction was abolished by preheating the SAP or by tr eating the cells with cycloheximide, Treatment with interleukins (IL) IL-1 or IL-6 or dexamethasone alone was ineffective. Combination of IL -1 with IL-6 was also ineffective, Combination of IL-6 with dexamethas one resulted in strong induction of the lithostathine/reg gene, but th e further addition of IL-1 to the mixture reduced induction, Treatment with tumor necrosis factor-alpha (TNF alpha) or interferon-gamma (IFN gamma) induced lithostathine/reg mRNA expression, Combination of dexa methasone with TNF alpha or IFN gamma showed an inhibitory effect on l ithostathine/reg mRNA expression, These findings suggest that expressi on of the lithostathine/reg mRNA during acute pancreatitis could be me diated by specific combinations of cytokines and/or glucocorticoids. ( C) 1996 Academic Press, Inc.