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Research Article Free access | 10.1172/JCI114133
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110.
Find articles by Perlmutter, D. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110.
Find articles by May, L. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110.
Find articles by Sehgal, P. in: JCI | PubMed | Google Scholar
Published July 1, 1989 - More info
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.
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