Medical Department III, University Hospital Aachen, RWTH Aachen, Germany.
Semin Liver Dis. 2010 Aug;30(3):215-25. doi: 10.1055/s-0030-1255351. Epub 2010 Jul 21.
Chemokines are a class of small chemotactic molecules with cytokine-like functions, which are well known to orchestrate inflammatory responses within different organs. Overall, more than 50 ligands and 19 receptors belong to the network. In recent years, accumulating functional and genetic evidence suggests that chemokines play a critical role in acute and chronic liver diseases, mediating the infiltration of immune cells (monocytes, T-cells) into the injured liver along a concentration gradient. However, chemokines can also directly affect the biology of liver resident cells, such as hepatic stellate cells and hepatocytes during inflammatory and fibrogenic tissue responses. Although the chemokine system has long been considered highly redundant, studies in knockout animals have convincingly demonstrated that single chemokines and chemokine receptors strongly affect the phenotype of toxic and inflammatory liver disease in vivo. However, depending on the model, these effects can be harmful (proinflammatory, profibrogenic) or beneficial (antifibrotic). This aspect of chemokine biology must be understood before these molecules and their receptors are targeted for therapeutic purposes. Here, we summarize current knowledge on the genetic and functional importance of the chemokine network in injury and highlight their potential for intervening in the inflammation and fibrosis that drives liver disease progression.
趋化因子是一类具有细胞因子样功能的小分子趋化因子，它们在不同器官内的炎症反应中起着重要的调节作用。总的来说，超过 50 种配体和 19 种受体属于这个网络。近年来，越来越多的功能和遗传证据表明，趋化因子在急性和慢性肝病中发挥着关键作用，介导免疫细胞（单核细胞、T 细胞）沿着浓度梯度浸润受损的肝脏。然而，趋化因子也可以直接影响肝脏驻留细胞（如肝星状细胞和肝细胞）的生物学特性，在炎症和纤维化组织反应中。尽管趋化因子系统长期以来被认为具有高度冗余性，但在基因敲除动物中的研究令人信服地表明，单一的趋化因子和趋化因子受体强烈影响体内毒性和炎症性肝病的表型。然而，根据模型的不同，这些效应可能是有害的（促炎、促纤维化），也可能是有益的（抗纤维化）。在针对这些分子及其受体进行治疗之前，必须了解趋化因子生物学的这一方面。在这里，我们总结了趋化因子网络在损伤中的遗传和功能重要性的最新知识，并强调了它们在干预驱动肝病进展的炎症和纤维化方面的潜力。
