IDENTIFICATION OF THE IL-6-RESPONSIVE ELEMENT IN AN ACUTE-PHASE-RESPONSIVE HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR-ENCODING GENE

Pancreatic secretory trypsin inhibitor (PSTI) has been suggested to be an acute-phase reactant in humans and to be induced by inflammatory c ytokines such as the interleukins IL-1 and IL-6. We report that PSTI i s synthesized in hepatoma cells and that the gene expression is augmen ted by IL-6. The start points (tsp) for basal and augmented transcript ion are exactly the same as the tsp in normal pancreas. Analysis of th e PSTI gene revealed that a 40-bp DNA fragment located between kb - 3. 84 and - 3.80 carries the element responsible for both basal transcrip tional activity and IL-6-induced gene expression. This 40-bp fragment contains T(G)T(NNGNAA)G(T), the consensus sequence for the NF-IL6-bind ing site, which is also known as the IL-6-responsive element that is c onserved among various acute-phase genes. The basal activity was augme nted by another sequence that lies between kb - 4.0 and - 3.9.