Interleukin-1beta induces macrophage inflammatory protein-1beta 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-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.
Zhang
Ting
T
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.
Guo
Chang-Jiang
CJ
Li
Yuan
Y
Douglas
Steven D
SD
Qi
Xiao-Xue
XX
Song
Li
L
Ho
Wen-Zhe
WZ
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
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