Interferon β2/interleukin 6 modulates synthesis of α₁-antitrypsin in human mononuclear phagocytes and in human hepatoma cells

The cytokine IFN β2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. IFN β2/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 β2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein α₁-antitrypsin (α₁ AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN β2/IL-6 each mediate a specific increase in steady-state levels of α₁ AT mRNA and a corresponding increase in net synthesis of α₁ AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN β2/IL-6 on α₁ AT gene expression in these cells is primarily due to an increase in accumulation of α₁ 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 β2/IL-6 regulates acute phase gene expression, specifically α₁ AT gene expression, in extrahepatic as well as hepatic cell types.