Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells.
The cytokine IFN beta 2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes. Accordingly, we have examined the effect of IFN beta 2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein alpha 1-antitrypsin (alpha 1 AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN beta 2/IL-6 each mediate a specific increase in steady-state levels of alpha 1 AT mRNA and a corresponding increase in net synthesis of alpha 1 AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN beta 2/IL-6 on alpha 1 AT gene expression in these cells is primarily due to an increase in accumulation of alpha 1 AT mRNA and can be distinguished from the direct, predominantly translational effect of bacterial lipopolysaccharide on expression of this gene in monocytes and macrophages. The results indicate that IFN beta 2/IL-6 regulates acute phase gene expression, specifically alpha 1 AT gene expression, in extrahepatic as well as hepatic cell types.
Perlmutter
D H
DH
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110.
May
L T
LT
Sehgal
P B
PB
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008113:Liver Neoplasms; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D012313:RNA