Fang Min, Dai Hong, Yu Guang, Gong Feili
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cell Mol Immunol. 2005 Oct;2(5):373-7.
Suppressor of cytokine signaling 3 (SOCS3) was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shock effect of liposome mediated gene delivery of SOCS3 in a lethal endotoxic shock mouse model. BALB/c mice were injected intraperitoneally with 200 microg pcDNA3.1-SOCS3 cationic liposomes, while pcDNA3.1-IL-10 and empty vector as positive and negative control respectively. Forty-eight hours after gene delivery, mice were challenged with 4 microg of E.coli 0127:B8 LPS and 18 mg D-GalN administered i.p. 90 min later, serum TNF-alpha level was determined. Survival over the next 48 h was evaluated. Peritoneal macrophages from survival mice were stimulated in vitro with 1 ug/ml LPS for 18 h, and the supernatants were harvested for determination of the amount of TNF-alpha. We found that gene delivery of SOCS3 significantly increase the mouse survival rate from 27.8 +/- 9.6% of control group to 61.1 +/- 9.6% (p < 0.01). In comparison with control group (218 +/- 13 pg/ml) and sham delivery group (2,122 pg/ml), gene delivery of SOCS3 reduced the level of serum TNF-alpha (68 +/- 9 pg/ml) significantly (p < 0.01). Furthermore, gene delivery of SOCS3 displayed the capacity of prevention of tolerance of peritoneal macrophages to LPS. These findings suggest that gene delivery of SOCS3 mediated by liposome is a promising approach for endotoxic septic shock treatment.
细胞因子信号转导抑制因子3（SOCS3）被报道为通过抑制JAK-STAT信号转导途径来反馈抑制细胞因子受体信号传导。我们试图在致死性内毒素休克小鼠模型中测试脂质体介导的SOCS3基因递送的抗内毒素性脓毒症休克作用。将BALB/c小鼠腹腔注射200微克pcDNA3.1-SOCS3阳离子脂质体，而分别将pcDNA3.1-IL-10和空载体作为阳性和阴性对照。基因递送48小时后，用4微克大肠杆菌0127：B8 LPS对小鼠进行攻击，90分钟后腹腔注射18毫克D-半乳糖胺，测定血清肿瘤坏死因子-α（TNF-α）水平。评估接下来48小时内的存活率。将存活小鼠的腹腔巨噬细胞在体外用1微克/毫升LPS刺激18小时，收集上清液以测定TNF-α的量。我们发现，SOCS3基因递送显著提高了小鼠存活率，从对照组的27.8±9.6%提高到61.1±9.6%（p<0.01）。与对照组（218±13皮克/毫升）和假递送组（2122皮克/毫升）相比，SOCS3基因递送显著降低了血清TNF-α水平（68±9皮克/毫升）（p<0.01）。此外，SOCS3基因递送显示出预防腹腔巨噬细胞对LPS产生耐受的能力。这些发现表明，脂质体介导的SOCS3基因递送是治疗内毒素性脓毒症休克的一种有前景的方法。
