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: Ting Zhang, Chang-Jiang Guo, Yuan Li, Steven D Douglas, Xiao-Xue Qi, Li Song, Wen-Zhe Ho
• Journal: Cellular immunology (Cell Immunol) Vol. 226 Issue 1 Pg. 45-53 (Nov 2003) ISSN: 0008-8749 [Print] Netherlands
• PMID: 14746807 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Caffeic Acids
• Chemokine CCL4
• Interleukin-1
• Macrophage Inflammatory Proteins
• NF-kappa B
• Receptors, CCR5
• caffeic acid phenethyl ester
• Phenylethyl Alcohol

Topics

• Caffeic Acids (metabolism)
• Cell Line, Tumor
• Chemokine CCL4
• Gene Expression Regulation
• Hepatocytes (cytology, immunology, physiology)
• Humans
• Interleukin-1 (immunology)
• Macrophage Inflammatory Proteins (genetics, metabolism)
• Macrophages (cytology, metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Phenylethyl Alcohol (analogs & derivatives, metabolism)
• Promoter Regions, Genetic
• Receptors, CCR5 (genetics, metabolism)