Schooltink H, Stoyan T, Roeb E, Heinrich P C, Rose-John S
Institut für Biochemie der RWTH Aachen, Germany.
FEBS Lett. 1992 Dec 21;314(3):280-4. doi: 10.1016/0014-5793(92)81489-9.
During inflammatory states, hepatocytes are induced to synthesize and secrete a group of proteins called acute-phase proteins. It has recently been shown that besides interleukin-6 (IL-6), related cytokines such as leukemia inhibitory factor, oncostation M and interleukin-11 are also mediators of the hepatic acute-phase response. All these mediators belong to the hematopoietic family of alpha-helical cytokines. Here we show that an additional member of this cytokine family, ciliary neurotrophic factor (CNTF), induces the hepatic acute-phase protein genes haptoglobin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and beta-fibrinogen in human hepatoma cells (HepG2) and in primary rat hepatocytes with a time course and dose-response comparable with that of IL-6. Our next aim was to define the receptor components used by CNTF on hepatic cells. Using a cell-free binding assay we exclude that CNTF binds to the 80 kDa IL-6 receptor, a protein with significant homology to the CNTF receptor which has recently been cloned from neuroblastoma cells. In human hepatoma cells (Hep3B) which lack the leukemia inhibitory factor receptor, CNTF was not able to induce acute-phase protein synthesis, indicating that this receptor protein may be part of the functional CNTF receptor on hepatic cells.
在炎症状态下，肝细胞被诱导合成并分泌一组称为急性期蛋白的蛋白质。最近研究表明，除白细胞介素-6（IL-6）外，白血病抑制因子、制瘤素M和白细胞介素-11等相关细胞因子也是肝脏急性期反应的介质。所有这些介质都属于α-螺旋细胞因子的造血因子家族。在此我们表明，该细胞因子家族的另一个成员，睫状神经营养因子（CNTF），在人肝癌细胞（HepG2）和原代大鼠肝细胞中诱导急性期蛋白基因触珠蛋白、α1-抗糜蛋白酶、α2-巨球蛋白和β-纤维蛋白原，其时间进程和剂量反应与IL-6相当。我们的下一个目标是确定CNTF在肝细胞上使用的受体成分。通过无细胞结合试验，我们排除了CNTF与80 kDa IL-6受体结合，该蛋白与最近从神经母细胞瘤细胞中克隆的CNTF受体具有显著同源性。在缺乏白血病抑制因子受体的人肝癌细胞（Hep3B）中，CNTF无法诱导急性期蛋白合成，表明该受体蛋白可能是肝细胞上功能性CNTF受体的一部分。
