RAT CONTRAPSINS ARE THE TYPE-II ACUTE-PHASE PROTEINS - REGULATION BY INTERLEUKIN-6 ON THE MESSENGER-RNA LEVEL

Three highly homologous serine protease inhibitors, SPI-1, SPI-2 and S PI-3 (contrapsins), are synthesized in rat liver. Their expression is regulated differently in healthy and inflamed animals. We found that i nterleukin 6 (IL-6), a major acute phase cytokine, and to a lesser ext ent leukemia inhibitory factor (LIF), both together with glucocorticoi ds, are responsible for the regulation of expression of the contrapsin s in rat hepatocytes in primary culture. The effect of IL-6 is time- a nd dose-dependent. IL-1, TGF beta(1), HGF, PMA and IL-8 did not have a ny effect on contrapsin mRNA levels. We postulate that SPI-1, SPI-2 an d SPI-3 belong to the class II acute phase proteins. Additionally, we show induction of SPI-3 mRNA in rat liver by in situ hybridization usi ng a specific oligonucleotide probe. (C) 1994 Academic Press, Inc.