title: Interleukin-1beta induces macrophage inflammatory protein-1beta expression in human hepatocytes.
abstract: 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-1beta (IL-1beta), a multifunctional cytokine, in regulating the expression of macrophage inflammatory protein (MIP)-1beta in human hepatocytes (Huh7 and HepG2). IL-1beta significantly enhanced MIP-1beta expression in these cells at both the mRNA and protein levels. Cytokine-enriched supernatants from monocyte-derived macrophage (MDM) cultures also induced MIP-1beta expression. IL-1beta is responsible for MDM supernatant-mediated up-regulation of MIP-1beta since the antibody to IL-1beta abolished MDM supernatant action. Investigation of the mechanism involved in MIP-1beta induction by IL-1beta showed that IL-1beta activated the nuclear factor kappa B (NF-kappaB) promoter in Huh7 cells. In addition, caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-kappaB, not only abolished IL-1beta-mediated NF-kappaB promoter activation, but also blocked IL-1beta-induced MIP-1beta expression. These observations suggest that IL-1beta-mediated up-regulation of MIP-1beta production in the hepatic cells may contribute a critical mechanism for continuous recruitment of inflammatory cell to liver and maintenance of inflammation.
authors.affiliation: Division of Allergy and Immunology, Joseph Strokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D002109:Caffeic Acids / Q000378:metabolism; D045744:Cell Line, Tumor; D054407:Chemokine CCL4; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D054407:Chemokine CCL4; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D019713:Receptors, CCR5; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol