Interferon β 2/B-Cell Stimulatory Factor Type 2 Shares Identity with Monocyte-Derived Hepatocyte-Stimulating Factor and Regulates the Major Acute Phase Protein Response in Liver Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 20; pp. 7251 - 7255
• Main Authors: Gauldie, Jack, Richards, Carl, Harnish, Del, Lansdorp, Peter, Baumann, Heinz
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-10-1987; National Acad Sciences
• Subjects: Acute phase proteins; Acute-Phase Proteins - biosynthesis; Animals; Antibodies; Antibodies - immunology; B lymphocytes; Carcinoma, Hepatocellular; Cytokines; Fibroblasts; Fibroblasts - analysis; Gene Expression Regulation - drug effects; Hep G2 cells; Hepatocytes; Humans; Inflammation - physiopathology; Interferon Type I - pharmacology; Interleukin-6; Leukocytes, Mononuclear - analysis; Liver - metabolism; Liver - physiopathology; Liver Neoplasms; Liver Neoplasms, Experimental; Molecules; Monocytes; Neoplasm Proteins - biosynthesis; Proteins - isolation & purification; Proteins - pharmacology; Rats; Recombinant Proteins - pharmacology; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.20.7251

One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon β 2 (IFN-β 2), which has been cloned. Antibodies raised against fibroblast-derived IFN-β having neutralizing activity against both IFN-β 1 and -β 2 inhibited the major hepatocyte-stimulating activity derived from monocytes. Fibroblast-derived mediator elicited the identical stimulated response in human HepG2 cells and primary rat hepatocytes as the monocyte cytokine. Finally, recombinant-derived human B-cell stimulatory factor type 2 (IFN-β 2) from Escherichia coli induced the synthesis of all major acute phase proteins studied in human hepatoma HepG2 and primary rat hepatocyte cultures. These data demonstrate that monocyte-derived hepatocyte-stimulating factor and IFN-β 2 share immunological and functional identity and that IFN-β 2, also known as B-cell stimulatory factor and hybridoma plasmacytoma growth factor, has the hepatocyte as a major physiologic target and thereby is essential in controlling the hepatic acute phase response.