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Alpha‐ and gamma‐interferon (IFNα, IFNγ) but not interleukin‐1 (IL‐1) modulate synthesis and secretion of β 2 ‐microglobulin by hepatocytes
Author(s) -
RAMADORI G.,
MITSCH A.,
RIEDER H.,
BÜSCHENFELDE K.H. MEYER ZUM
Publication year - 1988
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1988.tb01022.x
Subject(s) - beta 2 microglobulin , interferon , secretory protein , biology , interferon gamma , secretion , albumin , microbiology and biotechnology , cytokine , chemistry , endocrinology , immunology
Soluble serum β‐microglobulin has been thought to result from membrane shedding by activated T‐lymphocytes. This hypothesis could explain the increase of β 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 β 2 ‐microglobulin is a true secretory protein, and that its synthesis in hepatocytes is modulated by IFNs but not by IL‐1. While the 45000 MW HLA antigen can be found only in cell lysates, β 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 (IFNα) as well as interferon gamma (IFNγ) directly stimulate, in a dose‐and time‐dependent manner, β 2 ‐microglobulin synthesis by human hepatoma cells (Mz‐Hep‐1 and PLC/PRF5) and murine hepatocyte primary cultures. The increase of β 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 β 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 β 2 ‐M biosynthesis rate. These data indicate that (i) β 2 ‐microglobulin is a secretory protein, (ii) IFNs but not IL‐1 can mediate increased β 2 ‐M serum levels, and (iii) the liver may be its primary source.