Regulation of β2-microglobulin expression in different human cell lines by proinflammatory cytokines

Abstract

Background. Proinflammatory monocytic cytokines such as interleukin-1 (IL-1), tumour necrosis factor-α (TNF-α) and IL-6 have been incriminated in the pathogenesis of elevated β2-microglobulin (β2M) serum concentrations in patients undergoing haemodialysis with so-called bioincompatible dialyser membranes. However, neither the source of the elevated serum β2M nor the precise role of monocytic cytokines in the expression of the β2M 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 β2M 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-1β, IL-6, interferon-α (IFN-α), IFN-γ or conditioned media from lipopolysaccharide (LPS)-treated monocytes. Expression of β2M mRNA was analysed by Northern blotting, β2M protein synthesis was determined by metabolic labelling and immunoprecipitation, and β2M secretion was measured by an enzyme-linked immunosorbent assay (ELISA). Results. In all cell types tested, IFN-γ and, to a lesser extent, IFN-α stimulated gene expression of β2M resulting in an increased synthesis and secretion of β2M protein. Neither IL-1β and IL-6 nor supernatants from LPS-treated monocytes were capable of inducing β2M gene expression, with the exception of a small increase in HuH7 hepatoma cells upon IL-1β treatment. Conclusions. The present study provides evidence that interferons are important regulators of β2M expression. It also shows that proinflammatory monocytic cytokines do not modulate directly the expression of β2M in cells of hepatic, monocytic and T-lymphocytic origin. Whether they influence β2M synthesis and secretion indirectly by modulating interferon synthesis needs to be elucidated.