title: Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury.
abstract: 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.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.forename: Bao-Jun
authors.initials: BJ
authors.lastname: Huang
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Huang
authors.forename: Ping
authors.initials: P
authors.lastname: Xiong
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Yi-Fa
authors.initials: YF
authors.lastname: Chen
authors.forename: Fei-Li
authors.initials: FL
authors.lastname: Gong
mesh_terms: D000818:Animals; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012995:Solubility; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D052096:Warm Ischemia; D000093242:Interleukin-6 Inhibitors
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C486189:Il1rl1 protein, mouse; C493487:Tlr4 protein, mouse