Nephrol Dial Transplant (1999) 14: 2137-2143
© 1999 European Renal Association-European Dialysis and Transplant Association
Regulation of ß2-microglobulin expression in different human cell lines by proinflammatory cytokines
1 Institut für Biochemie, 2 Medizinische Klinik II and 3 Interdisziplinäres Zentrum für Klinische Forschung BIOMAT, Rheinisch-Westfälische Technische Hochschule Aachen, D-52057 Aachen, Germany
Correspondence and offprint requests to: Thomas H. Ittel, MD, Chief, Department of Internal Medicine, Klinikum der Hansestadt Stralsund, Große Parowerstr. 47–53, D-18435 Stralsund, Germany.
Background. Proinflammatory monocytic cytokines such as interleukin-1 (IL-1), tumour necrosis factor-
(TNF-) and IL-6 have been incriminated in the pathogenesis of elevated ß2-microglobulin (ß2M) serum concentrations in patients undergoing haemodialysis with so-called bioincompatible dialyser membranes. However, neither the source of the elevated serum ß2M nor the precise role of monocytic cytokines in the expression of the ß2M gene have been elucidated conclusively. The aim of the current study was to evaluate whether monoytic cytokines, and in particular IL-6, are regulators of ß2M gene expression in human hepatoma cells, T-lymphocytes and monocytes.
Methods. HepG2 and HuH7 human hepatoma cells, Jurkat T-cells, monocytic MonoMac6 cells, primary human monocytes and synoviocytes were stimulated with IL-1ß, IL-6, interferon- (IFN-), IFN-
or conditioned media from lipopolysaccharide (LPS)-treated monocytes. Expression of ß2M mRNA was analysed by Northern blotting, ß2M protein synthesis was determined by metabolic labelling and immunoprecipitation, and ß2M secretion was measured by an enzyme-linked immunosorbent assay (ELISA).
Results. In all cell types tested, IFN- and, to a lesser extent, IFN- stimulated gene expression of ß2M resulting in an increased synthesis and secretion of ß2M protein. Neither IL-1ß and IL-6 nor supernatants from LPS-treated monocytes were capable of inducing ß2M gene expression, with the exception of a small increase in HuH7 hepatoma cells upon IL-1ß treatment.
Conclusions. The present study provides evidence that interferons are important regulators of ß2M expression. It also shows that proinflammatory monocytic cytokines do not modulate directly the expression of ß2M in cells of hepatic, monocytic and T-lymphocytic origin. Whether they influence ß2M synthesis and secretion indirectly by modulating interferon synthesis needs to be elucidated.
Keywords: bioincompatibility; cytokines; hepatoma cells; interleukin-6; long-term haemodialysis; ß2-microglobulin amyloidosis
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