Induction of lithostathine/reg mRNA expression by serum from rats 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 and lithostathine/reg increase dramatically, In the present study we have 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-dependent manner, Induction was abolished by preheating the SAP or by treating 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 dexamethasone resulted in strong induction of the lithostathine/reg gene, but the 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 dexamethasone with TNF alpha or IFN gamma showed an inhibitory effect on lithostathine/reg mRNA expression, These findings suggest that expression of the lithostathine/reg mRNA during acute pancreatitis could be mediated by specific combinations of cytokines and/or glucocorticoids. (C) 1996 Academic Press, Inc.