Regulation of beta(2)-microglobulin expression in different human cell lines by proinflammatory cytokines

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 con centrations in patients undergoing haemodialysis with so-called bioincompat ible dialyser membranes. However, neither the source of the elevated serum beta(2)M nor the precise role of monocytic cytokines in the expression of t he beta(2)M gene have been elucidated conclusively. The aim of the current study was to evaluate whether monoytic cytokines, and in particular IL-6, a re regulators of beta(2)M gene expression in human hepatoma cells, T-lympho cytes 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-gam ma or conditioned media from lipopolysaccharide (LPS)-treated monocytes. Ex pression of beta(2)M mRNA was analysed by Northern blotting, beta(2)M prote in synthesis was determined by metabolic labelling and immunoprecipitation, and beta(2)M secretion was measured by an enzyme-linked immunosorbent assa y (ELISA). Results. In all cell types tested, IFN-gamma and, to a lesser ex tent, IFN-alpha stimulated gene expression of beta(2)M resulting in an incr eased 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 bet a(2)M gene expression, with the exception of a small increase in HuH7 hepat oma 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 dir ectly the expression of beta(2)M in cells of hepatic, monocytic and T-lymph ocytic origin. Whether they influence beta(2)M synthesis and secretion indi rectly by modulating interferon synthesis needs to be elucidated.