Yin Hui, Huang Bao-Jun, Yang Heng, Huang Ya-Fei, Xiong Ping, Zheng Fang, Chen Xiao-Ping, Chen Yi-Fa, Gong Fei-Li
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' Republic of China.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):940-6. doi: 10.1016/j.bbrc.2006.10.166. Epub 2006 Nov 7.
The interleukin-1 receptor-like protein ST2 exists in both membrane-bound (ST2L) and soluble form (sST2). ST2L has been found to play an important regulatory role in Th2-type immune response, but the function of soluble form of ST2 remains to be elucidated. In this study, we report the protective effect of soluble ST2 on warm hepatic ischemia/reperfusion injury. We constructed a eukaryotic expression plasmid, psST2-Fc, which expresses functional murine soluble ST2-human IgG1 Fc (sST2-Fc) fusion protein. The liver damage after ischemia/reperfusion was significantly attenuated by the expression of this plasmid in vivo. sST2-Fc remarkably inhibited the activation of Kupffer cells and the production of proinflammatory mediators TNF-alpha and IL-6. Furthermore, the levels of TLR4 mRNA and the nuclear translocation of NF-kappaB were also suppressed by pretreatment with sST2-Fc. These results thus identified soluble ST2 as a negative regulator in hepatic I/R injury, possibly via ST2-TLR4 pathway.
白细胞介素-1受体样蛋白ST2以膜结合形式（ST2L）和可溶性形式（sST2）存在。已发现ST2L在Th2型免疫反应中起重要调节作用，但ST2可溶性形式的功能仍有待阐明。在本研究中，我们报道了可溶性ST2对肝脏热缺血/再灌注损伤的保护作用。我们构建了一个真核表达质粒psST2-Fc，其表达功能性小鼠可溶性ST2-人IgG1 Fc（sST2-Fc）融合蛋白。该质粒在体内的表达显著减轻了缺血/再灌注后的肝损伤。sST2-Fc显著抑制了库普弗细胞的激活以及促炎介质TNF-α和IL-6的产生。此外，sST2-Fc预处理还抑制了TLR4 mRNA水平和NF-κB的核转位。因此，这些结果确定可溶性ST2可能通过ST2-TLR4途径在肝脏缺血/再灌注损伤中作为负调节因子。
