Alpha‐ and gamma‐interferon (IFNα, IFNγ) but not interleukin‐1 (IL‐1) modulate synthesis and secretion of β2‐microglobulin by hepatocytes

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Abstract
Soluble serum .beta.-2-microglobulin has been thought to result from membrane shedding by activated T-lymphocytes. This hypothesis could explain the increase of .beta.2-microglobulin serum levels during virally induced mononucleosis, but not elevated levels as observed in other virally induced and in malignant diseases. In this paper we demonstrate that .beta.2-microglobulin is a true secretory protein, an d that its synthesis in hepatocytes is modulated by IFNs but not by IL-1. While the 45,000 MW HLA antigen can be found only in cell lysates, .beta.2-microglobulin is shown to be secreted also into the culture medium like other secretory proteins (e.g. albumin-factor B-complement C3). Furthermore, interferon alpha (IFN.alpha.) as well as interferon gamma (IFN.gamma.) directly stimulate, in a dose-and time-dependent manner, .beta.2-microglobulin synthesis by human hepatoma cells (Mz-Hep-1 and PLC/ PRF5) and murine hepatocyte primary cultures. The increase of .beta.2-microglobulin production induced by interferons is demonstrated at both the protein and the RNA level, indicating that interferon acts at a pretranslational level. The interferon effect on .beta.2-microglobulin synthesis is specific since synthesis of secretory proteins like complement C3 or albumin, and of a structural protein like actin, remains unchanged. In contrast to IFN, IL-1, the main mediator of acute phase response, does not change .beta.2-M biosynthesis rate. These data indicate that (i) .beta.2-microglobulin is a secretory protein, (ii) IFNs but not IL-1 can mediate increased .beta.2-M serum levels, and (iii) the liver may be its primary source.