Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome.
Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome.
复制标题
腹泻型肠易激综合征中 Toll 样受体 4/核因子-κ B 对炎症的调节
DOI：
10.18632/oncotarget.23045
复制
发表时间：
2017-12-26
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
He X;Cui LH;Wang XH;Yan ZH;Li C;Gong SD;Zheng Y;Luo Z;Wang Y
为探讨TLR 4/NF-κB信号通路在肠易激综合征（IBS-D）发病机制中的作用，采用急性应激和慢性应激（29 d）建立Wistar大鼠IBS-D动物模型。未进行应激攻击的Wistar大鼠用作对照。将IBS-D模型随机分为两组，一组给予生理盐水，另一组给予TLR 4/NF-κB抑制剂二硫代氨基甲酸吡咯烷酯（PDTC）50 mg/kg/周，连续4次。我们的研究结果表明，持续的压力可以诱发IBS-D的特征性症状，包括高湿便率和肠道植物群失衡。进一步检测结肠组织中TLR 4和NF-κB的蛋白表达水平，IBS-D组均高于对照组。IBS-D组IL-8、TNFα和MyD 88的分泌水平明显升高。给予PDTC可有效下调这些炎症因子的水平。而IL-10则相反，IBS-D组IL-10水平较低，PDTC治疗后IL-10水平升高至对照组水平。PDTC抑制TLR 4/NF-κB表达，主要通过增加肠绒毛高度改善肠黏膜微结构。结果提示，TLR 4/NF-κB信号通路在IBS-D炎症反应的调控中起重要作用，可能成为IBS-D的治疗靶点。所有这些发现也提供了关于应激/NF-κB/炎症轴与IBS-D之间内在联系的证据。
In order to investigate the function of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal pathways in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar rats challenged with acute and chronic stresses (29 days). Wistar rats without stress-challenged were used as controls. IBS-D models were randomly divided into two groups: one was treated with normal saline, another group was treated with TLR4/NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for continuous four times. Our results demonstrate that continuous stresses can induce the characteristic symptoms of IBS-D, including high wet stool rate and intestinal flora imbalance. Further examinations of colon tissues show that the protein expression levels of TLR4 and NF-κB in IBS-D groups are higher than that in control group. The secretory levels of interleukin (IL-8), tumor necrosis factor α (TNFα), and myeloid differentiation factor 88 (MyD88) are significantly increased in IBS-D group. Administration with PDTC effectively downregulates levels of these inflammatory factors. In contrast, interleukin-10 (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the PDTC treatment increases it to the levels as in control group. Moreover, inhibition of the TLR4/NF-κB by PDTC improves the microstructure of intestinal mucosa mainly by increasing the height of villi. Our results suggest that TLR4/NF-κB signal pathway plays an important role in the modulation of inflammatory responses in IBS-D, which might be a therapeutic target for the IBS-D. All of these findings also provide the evidence concerning an inherent linkage between the axis of stress/NF-κB/inflammation and IBS-D.
登录
查看更多内容
影响因子：
30.5
作者：
Xing Y;Wang X;Jameson SC;Hogquist KA
通讯作者：
Hogquist KA
影响因子：
82.9
作者：
Rousseaux, Christel;Thuru, Xavier;Desreumaux, Pierre
通讯作者：
Desreumaux, Pierre
影响因子：
4.3
作者：
Lee, Kang Nyeong;Lee, Oh Young
通讯作者：
Lee, Oh Young
DOI：
10.1016/j.nicl.2017.06.001
发表时间：
2017
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Icenhour A;Witt ST;Elsenbruch S;Lowén M;Engström M;Tillisch K;Mayer EA;Walter S
通讯作者：
Walter S
Pannexin-1 通道在大鼠实验性蛛网膜下腔出血后通过 TLRs/NF-Kappa B 信号通路的炎症反应中的作用。
影响因子：
4.8
作者：
Wu LY;Ye ZN;Zhou CH;Wang CX;Xie GB;Zhang XS;Gao YY;Zhang ZH;Zhou ML;Zhuang Z;Liu JP;Hang CH;Shi JX
通讯作者：
Shi JX