Untersuchungen zur Rolle von Zytokinen bei der Beta-2-Mikroglobulin-Synthese in verschiedenen humanen Zelltypen
Background. Proinflammatory monocytic cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and IL-6 have been incriminated in the pathogenesis of elevated beta-2-microglobulin (beta-2-M) serum concentrations in patients undergoing haemodialysis with so-called bioincompatible dialyser membranes. However, neither the source of the elevated serum beta-2-M nor the precise role of monocytic cytokines in the expression of the beta-2-M gene have been elucidated conclusively. The aim of this study was to evaluate whether monoytic cytokines, and in particular IL-6, are regulators of beta-2-M 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-1-beta, IL-6, interferon-alpha (IFN-alpha), IFN-gamma or conditioned media from lipopolysaccharide (LPS)-treated monocytes. Expression of beta-2-M mRNA was analysed by Northern blotting, beta-2-M protein synthesis was determined by metabolic labelling and immunoprecipitation, and beta-2-M secretion was measured by an enzyme-linked immunosorbent assay (ELISA). Results. In all cell types tested, IFN-gamma and, to a lesser extent, IFN-alpha stimulated gene expression of beta-2-M resulting in an increased synthesis and secretion of beta-2-M protein. Neither IL-1-beta and IL-6 nor supernatants from LPS-treated monocytes were capable of inducing beta-2-M gene expression, with the exception of a small increase in HuH7 hepatoma cells upon IL-1-beta treatment. Conclusions. The present study provides evidence that interferons are important regulators of beta-2-M expression. It also shows that proinflammatory monocytic cytokines do not modulate directly the expression of beta-2-M in cells of hepatic, monocytic and T-lymphocytic origin. Whether they are other inflammatory influences to the bioincompability of dialyser membranes is discussed in this study.
info:eu-repo/classification/ddc/610, Amyloidose, Mikroglobulin <beta-2->, Dialyse, Interleukin 6, Interleukin 1, Interferon <gamma->, Interferon, Interferon <alpha->, Medizin, Bioinkompatibilität, Zytokine, Hämodialyse, Beta-2-Mikroglobulin, bioincompatibility, cytokines, haemodialysis, beta-2-microglobulin, amyloidosis
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