Alpha- and gamma-interferon (IFN alpha, IFN gamma) but not interleukin-1 (IL-1) modulate synthesis and secretion of beta 2-microglobulin by hepatocytes.
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, and 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.
Ramadori
G
G
I. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universität Mainz, FRG.
Mitsch
A
A
Rieder
H
H
Meyer zum Büschenfelde
K H
KH
D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis; D011415:Complement Factor B / Q000096:biosynthesis; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism
D000418:Albumins; D003176:Complement C3; D007375:Interleukin-1; D001613:beta 2-Microglobulin; D007372:Interferons; D011415:Complement Factor B