SYNTHESIS OF ALPHA-1-MICROGLOBULIN IN CULTURED RAT HEPATOCYTES IS STIMULATED BY INTERLEUKIN-6, LEUKEMIA INHIBITORY FACTOR, DEXAMETHASONE AND RETINOIC ACID

The secretion of alpha-1-microglobulin by primary cultures of rat hepatocytes was found to increase upon the addition of interleukin-6 or leukemia inhibitory factor, two mediators of acute phase response. This stimulatory effect was further enhanced by dexamethasone. Alpha-1-microglobulin is synthesized as a precursor also containing bikunin, and the precursor protein is cleaved shortly before secretion. Our results therefore suggest that both alpha-1-microglobulin and bikunin are acute phase reactants in rat hepatocytes. Furthermore, we found that retinoic acid, previously shown to be involved in the regulation of cell differentiation and development, also stimulated alpha-1-microglobulin synthesis. Only free, uncomplexed alpha-1-microglobulin (28,000 Da) was detected in the hepatocyte media, suggesting that the complex between alpha-1-microglobulin and alpha-1-inhibitor 3, found in rat serum, is formed outside the hepatocyte.