Zhang Ting, Guo Chang-Jiang, Li Yuan, Douglas Steven D, Qi Xiao-Xue, Song Li, Ho Wen-Zhe
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.
Cell Immunol. 2003 Nov;226(1):45-53. doi: 10.1016/j.cellimm.2003.10.005.
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.
CC趋化因子是免疫反应和炎症过程中的重要介质，对调控其表达的因素进行研究，对于理解肝脏疾病的免疫发病机制具有重要意义。我们检测了多功能细胞因子白细胞介素-1β（IL-1β）在调控人肝细胞（Huh7和HepG2）中巨噬细胞炎性蛋白（MIP）-1β表达方面的作用。IL-1β在mRNA和蛋白质水平均显著增强了这些细胞中MIP-1β的表达。来自单核细胞衍生巨噬细胞（MDM）培养物的富含细胞因子的上清液也可诱导MIP-1β表达。IL-1β介导了MDM上清液对MIP-1β的上调作用，因为抗IL-1β抗体消除了MDM上清液的作用。对IL-1β诱导MIP-1β的机制研究表明，IL-1β激活了Huh7细胞中的核因子κB（NF-κB）启动子。此外，NF-κB激活的特异性抑制剂咖啡酸苯乙酯（CAPE）不仅消除了IL-1β介导的NF-κB启动子激活，还阻断了IL-1β诱导的MIP-1β表达。这些观察结果表明，IL-1β介导的肝细胞中MIP-1β产生的上调可能是炎症细胞持续募集到肝脏并维持炎症的关键机制。
