Wasmuth H E, Weiskirchen R
Medizinische Klinik III, Universitätsklinikum Aachen, RWTH Aachen.
Z Gastroenterol. 2010 Jan;48(1):38-45. doi: 10.1055/s-0028-1109933. Epub 2010 Jan 13.
Liver fibrosis is the common sequel of chronic liver diseases and is associated with high morbidity and mortality in affected patients. In recent years, the contribution of chemokines and their receptors to liver fibrosis has been delineated. Chemokines are a family of chemotactic and immunomodulatory molecules that act through different G-protein coupled receptors on target cells. Apart from their classical function of regulating immune cell recruitment during chronic liver injury, chemokines can directly affect the function of hepatic stellate cells within the liver. Up to now, nine of the 19 known chemokine receptors have been characterised on stellate cells. Stimulation of most of these receptors with specific ligands leads to increased migration and proliferation of stellate cells, suggesting predominantly profibrotic effects of chemokines. The only chemokine receptor with potential antifibrotic effects identified so far is CXCR3. Notably, hepatic stellate cells are not only a target but also a source of chemokines which contributes to the direct interaction between stellate cells and other cells during fibrogenesis. The further characterisation of this interaction will yield new therapeutic options for the treatment of chronic liver diseases. In this respect chemokines are a valuable target as oral chemokine receptor antagonists have already been licensed for human use.
肝纤维化是慢性肝病的常见后遗症，与受影响患者的高发病率和死亡率相关。近年来，趋化因子及其受体对肝纤维化的作用已被阐明。趋化因子是一类趋化性和免疫调节分子，通过靶细胞上不同的G蛋白偶联受体发挥作用。除了在慢性肝损伤期间调节免疫细胞募集的经典功能外，趋化因子还可直接影响肝脏内肝星状细胞的功能。到目前为止，19种已知趋化因子受体中的9种已在星状细胞中得到表征。用特异性配体刺激这些受体中的大多数会导致星状细胞迁移和增殖增加，表明趋化因子主要具有促纤维化作用。迄今为止确定的唯一具有潜在抗纤维化作用的趋化因子受体是CXCR3。值得注意的是，肝星状细胞不仅是趋化因子的靶标，也是趋化因子的来源，这有助于在纤维化形成过程中星状细胞与其他细胞之间的直接相互作用。对这种相互作用的进一步表征将为慢性肝病的治疗带来新的治疗选择。在这方面，趋化因子是一个有价值的靶点，因为口服趋化因子受体拮抗剂已被批准用于人类。
