Schlaf G, Demberg T, Koleva M, Jungermann K, Götze O
Abteilung Immunologie, Georg-August-Universität Göttingen, Germany.
Biol Chem. 2001 Jul;382(7):1089-94. doi: 10.1515/BC.2001.137.
Complement factor I (FI) is a regulatory serine protease of the complement system which cleaves three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b and thus prevents the assembly of the C3 and C5 convertases. We have investigated the proinflammatory cytokines IL-6, IL-1beta, TNF-alpha and IFN-gamma for their potential role in the regulation of FI expression. Of the investigated cytokines, only IL-6 increased the FI-specific RT-PCR signal in isolated hepatocytes, in the two rat hepatoma-derived cell lines FAO and H4IIE or in HUVECs. Quantitative competitive RT-PCR showed an IL-6 induced upregulation of FI-specific mRNA by about ten-fold. These data are in accord with Northern blot analyses in which the FI-mRNA was upregulated by IL-6 between five- and seven-fold. IL-6, but not IL-1beta, TNF-alpha or IFN-gamma also increased FI-protein levels in cell culture supernatants by about five-fold as determined by a semiquantitative immunoblot using a novel monoclonal antibody specific for rat FI.
补体因子I（FI）是补体系统的一种调节性丝氨酸蛋白酶，它可切割C3bα链中的三个肽键以及C4bα链中的两个肽键，从而阻止C3和C5转化酶的组装。我们研究了促炎细胞因子白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）在调节FI表达中的潜在作用。在所研究的细胞因子中，只有IL-6在分离的肝细胞、两种大鼠肝癌衍生细胞系FAO和H4IIE或人脐静脉内皮细胞（HUVECs）中增加了FI特异性逆转录聚合酶链反应（RT-PCR）信号。定量竞争性RT-PCR显示，IL-6诱导FI特异性mRNA上调约10倍。这些数据与Northern印迹分析结果一致，在Northern印迹分析中，FI-mRNA被IL-6上调了5至7倍。通过使用一种针对大鼠FI的新型单克隆抗体进行的半定量免疫印迹测定，IL-6而非IL-1β、TNF-α或IFN-γ也使细胞培养上清液中的FI蛋白水平增加了约5倍。
