Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury.
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.
Yin
Hui
H
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' Republic of China.
Huang
Bao-Jun
BJ
Yang
Heng
H
Huang
Ya-Fei
YF
Xiong
Ping
P
Zheng
Fang
F
Chen
Xiao-Ping
XP
Chen
Yi-Fa
YF
Gong
Fei-Li
FL
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
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