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[1]黄 颖,曹 超,王 军,等.TLR4在脓毒症中对调节性T细胞功能活性的影响[J].天津医科大学学报,2018,24(06):492-495.
　HUANG Ying,CAO Chao,WANG Jun,et al.The effects of TLR4 on regulating the function of Tregs in sepsis[J].Journal of Tianjin Medical University,2018,24(06):492-495.
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
24卷
期数:
2018年06期
页码:
492-495
栏目:
基础医学
出版日期:
2018-11-20

文章信息/Info

Title:
The effects of TLR4 on regulating the function of Tregs in sepsis
作者:
黄 颖; 曹 超; 王 军; 寿松涛
（天津医科大学总医院急诊科，天津300052）
Author(s):
HUANG Ying; CAO Chao; WANG Jun; SHOU Song-tao
（Department of Emergency Medicine,General Hospital，Tianjin Medical University,Tianjin 300052,China）
关键词:
Toll样受体4; 调节性T细胞; 脓毒症; 信号通路
Keywords:
Toll-like receptor 4;  Treg;  Sepsis;  Signaling
分类号:
R631
DOI:
-
文献标志码:
A
摘要:
目的：探讨脓毒症中TLR4 （TLR4）对调节性T细胞功能及活性的影响,并探讨其作用机制。方法：SPF级C57/BL6雄性小鼠（wild type,WT）40只，C57BL/10ScNJNJU（TLR4-/-）小鼠40只，随机均分为4组，WTSham组，WTCLP组，TLR4-/-Sham组和TLR4-/-CLP。CLP组用盲肠结扎穿孔法制备脓毒症模型。造模后24 h，FCM检测脾脏CD4+CD25+Foxp3+Treg细胞数量、凋亡率及Foxp3和TLR4表达情况, RT-PCR检测Foxp3+mRNA和TLR4mRNA的表达,Western Blot检测Treg细胞内NF-κB、p-NF-κB蛋白表达情况。结果：（1） TLR4-/-CLP组Treg细胞凋亡率较WTCLP组明显增多,而细胞数量显著降低（P<0.05）。（2）WT CLP组Treg中Foxp3mRNA及蛋白表达、TLR4mRNA及蛋白水平显著升高（P<0.05），而在TLR4-/-CLP组中该表达较WT CLP组均显著降低（P<0.05）。（3） WT CLP组Treg细胞NF-κB、p-NF-κB的表达水平明显升高（P<0.05），而TLR4-/-CLP组较WT CLP组明显降低（P<0.05）。结论：在脓毒症中TLR4可显著影响Treg的功能及其活性，这可能通过TLR4/NF-κB信号通路介导有关。
Abstract:
Objective: To study the effects of TLR4 on regulating the function of Tregs in sepsis. Methods:Fortyhealthy male C57/BL mice（wild type,WT） and forty healthy male TLR4 knockout mice （TLR4-/-） were divided into Sham operation group （WT Sham group，n =20），WTCLP group （n=20），and TLR4-/-Sham group（n=20），TLR4-/-CLP group （n =20）by random number table method. In CLP group,the mice were given cecal ligation puncture（CLP），and in Sham group,the mice were given Sham-operation. Twenty-four hours after CLP,Tregnumber,Tregapoptsis rate, the expression of Foxp3 ,TLR4 at mRNA and protein level，the protein expression of NF-κB and p-NF-κB were determined. Results:（１） The apoptosis of Treg cells in TLR4-/-CLP group was higher than that in WTCLP group（P＜0.05）. （2） The levels of Foxp3mRNA and Foxp3 protein, TLR4mRNA and TLR4 protein in TLR4-/-CLP group were significantly lower than those in WTCLP group(P＜0.05）.（3）The expression of NF-κB and p-NF-κB in splenic Tregs was significantly increased in WT CLP mice in comparison to TLR4-/-CLP mice(P＜0.05）.Conclusion: TLR4 in experimental sepsiscloselyaligns with the function of Tregs, and this effect may be related to TLR4/NF-κB signaling.

参考文献/References:


[1] Singer M，Deutschman C S，Seymour C W， et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA，2016，315（8）:801
[2] Cheng B， Xie G， Yao S， et al. Epidemiology of sever sepsis in critically ill surgical patients in ten university hospitals in China[J]. Crit Care Med， 2007， 35（11）: 2538
[3] Okwor I，Onyilagha C，Kuriakose S， et al. Regulatory T cells enhance susceptibility to experimental Trypanosomacongolense infection Independent of mouse genetic background[J]. PLoS Negl Trop Dis，2012，6（7）:1761
[4] Nascimento D C，Alves-Filho J C，S?觝nego F， et al. Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis[J]. Crit Care Med，2010，38（8）:1718
[5] Dellinger R P，Levy M M，Carlet J M， et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008[J]. Intensive Care Med，2008，34（1）:17
[6] Deutschman C S，Tracey K J. Sepsis: current dogma and new perspectives[J]. Immunity，2014，40（4）:463
[7] BernardA M，Bernard G R. The immune response: targets for the treatment of severe sepsis[J]. Int J Inflam，2012:697592
[8] Fernandez R，Nardocci G，Navarro C， et al. Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy[J].Front Physiol，2014，5:489
[9] Markwart R，Condotta S A，Requardt R P， et al. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of na?觙ve T-cells but no enduring cell-autonomous defects in T-cell function[J]. PLoS One，2014，9（12）:e115094
[10] Rittirsch D，Huber-Lang M S，Flierl M A， et al. Immunodesign of experimental sepsis by cecal ligation and puncture[J]. Nat Protoc，2009，4（1）:31
[11] Yang J，Zhang J X，WangH，et al. Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppression via Treg requires TLR4 signaling[J].World J Gastroenterol，2012，18（23）:2938-2947.
[12] Huss D J，Pellerin A F，Collette B P，et al. Anti-CD25 monoclonal antibody Fc variants differentially impact Treg cells and immune homeostasis[J]. Immunology，2016.
[13] Doyle SL，O’Neil LA. Toll-like receptors:From the discovery of NF-κB to new insights into transcriptional regulations in innate immunity[J]. Biochem Pharmacol，2006，72（9）:1102
[14] Li T，Hu J，Thomas J A，et al.Differential induction of apoptosis by LPS and taxol in monocytic cells[J].Mol Immunol，2005，42（9）:1049
[15] Akira S，Takeda K.Toll-like receotorsignaling[J]. Nat Rev Immunol，2004，4（7）:499
[16] Zou L，Feng Y，Li Y， et al. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis[J]. J Immunol，2013，191（11）:5625
[17] Nagai Y，Akashi S，Nagafuku M， et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution[J]. Nat Immunol，2002，3（7）:667
[18] Muroi M，Ohnishi T，Tanamoto K I. Regions of the mouse CD14 molecule required for toll-like receptor 2- and 4-mediated activation of NF-kappa B[J]. J Biol Chem，2002，277（44）:42372
[19] Sharma S，Tenoever B R，Grandvaux N， et al. Triggering the interferon antiviral response through an IKK-related pathway[J]. Science，2003，300（5622）:1148
[20] 申鹏霄，王建生.雷米普利对阿霉素肾病大鼠肾脏Toll样受体4，核因子-κB，白细胞介素-8表达的影响[J].中华实用诊断与治疗杂志，2010，24（3）:250
[21] 司徒超，黄卫东，付秀丽，等.脓毒症患儿白细胞介素-6、血小板动态测定的临床意义[J].中华实用诊断与治疗杂志，2009，23（12）:1202

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备注/Memo

备注/Memo:
基金项目 天津市应用基础与前沿技术研究计划项目（13JCYBJC37500）；睿E（睿医）急诊医学研究专项基金项目（R2015026）；天普研究基金项目（UF201315）；天津医科大学总医院青年孵育基金项目（ZYYFY2015010）
作者简介 黄颖（1992-），女，硕士在读，研究方向：脓毒症；通信作者：寿松涛，E-mail:stshou66@sina.com。
更新日期/Last Update: 2018-11-30