Interleukin-1β induces macrophage inflammatory protein-1β expression in human hepatocytes

The investigation of factors that regulate expression of CC-chemokines, the important mediators in immune responses and inflammation processes, has an important significance in understanding the immunopathogenesis of liver diseases. We examined the role of interleukin-1β (IL-1β), a multifunctional cytokine, in regulating the expression of macrophage inflammatory protein (MIP)-1β in human hepatocytes (Huh7 and HepG2). IL-1β significantly enhanced MIP-1β expression in these cells at both the mRNA and protein levels. Cytokine-enriched supernatants from monocyte-derived macrophage (MDM) cultures also induced MIP-1β expression. IL-1β is responsible for MDM supernatant-mediated up-regulation of MIP-1β since the antibody to IL-1β abolished MDM supernatant action. Investigation of the mechanism involved in MIP-1β induction by IL-1β showed that IL-1β activated the nuclear factor kappa B (NF-κB) promoter in Huh7 cells. In addition, caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-κB, not only abolished IL-1β-mediated NF-κB promoter activation, but also blocked IL-1β-induced MIP-1β expression. These observations suggest that IL-1β-mediated up-regulation of MIP-1β production in the hepatic cells may contribute a critical mechanism for continuous recruitment of inflammatory cell to liver and maintenance of inflammation.