Synthesis of α1‐microglobulin in cultured rat hepatocytes is stimulated by interleukin‐6, leukemia inhibitory factor, dexamethasone and retinoic acid

The secretion or α1‐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. α1‐Microglobulin is synthesized as a precursor also containing bikunin, and the precursor protein is cleaved shortly berore secretion. Our results therefore suggest that both α1‐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 α1‐microglobulin synthesis. Only free, uncomplexed α1‐microglobulin (28,000 Da) was detected in the hopatocyte media, suggesting that the complex between α1‐microglobulin and α1‐inhibitor 3, found in rat serum, is formed outside the hepatocyte.