BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model.
BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model.
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BAFF 阻断可减轻小鼠内毒素血症模型中的炎症反应和肠屏障功能障碍
DOI：
10.3389/fimmu.2020.570920
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发表时间：
2020
影响因子：
7.3
通讯作者：
Fu Y
中科院分区：
文献类型：
--
作者：
Quan R;Chen C;Yan W;Zhang Y;Zhao X;Fu Y
B细胞活化因子（BAFF）的产生在脓毒症患者中增加。然而，BAFF在脓毒症中的具体作用尚不清楚。本研究旨在研究BAFF在实验性内毒素血症模型中的表达和功能，并确定其可能的机制。通过给药30 mg/kg脂多糖（LPS）建立内毒素血症小鼠（6-8周，20-22 g）模型。注射LPS后4和8 h分别测定循环系统和器官组织中的BAFF水平。BAFF阻断后72小时监测内毒素血症小鼠的存活率。在LPS处理4小时后，还评估了BAFF阻断对全身和局部炎症、器官损伤和肠屏障功能的影响。LPS刺激后，BAFF的生成在全身和局部均升高。BAFF阻断改善了生存率、全身炎症和多器官损伤。此外，BAFF阻断可减轻肠道炎症和肠通透性受损。BAFF阻断通过NF-κB/MLCK/MLC信号通路上调ZO-1和occludin蛋白水平。这些结果表明BAFF阻断至少部分通过减轻炎症、多器官损伤和改善肠屏障功能来保护致死性内毒素血症，并为进一步研究败血症提供了新的重点和临床治疗的实验证据。
B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.
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影响因子：
2.4
作者：
Bischoff SC;Barbara G;Buurman W;Ockhuizen T;Schulzke JD;Serino M;Tilg H;Watson A;Wells JM
通讯作者：
Wells JM
DOI：
10.1590/1414-431x20154853
发表时间：
2016-03-01
影响因子：
2.3
作者：
Duan, J.H.;Jiang, Y.;Tang, Z.Q.
通讯作者：
Tang, Z.Q.
影响因子：
38.9
作者：
Rhodes, Andrew;Evans, Laura E.;Dellinger, R. Phillip
通讯作者：
Dellinger, R. Phillip
体内多种微生物败血症期间紧密连接的破坏
影响因子：
7.3
作者：
Li, Qiurong;Zhang, Qiang;Li, Jieshou
通讯作者：
Li, Jieshou
影响因子：
7.5
作者：
Li, Zhiling;Gao, Ming;Yang, Mingshi
通讯作者：
Yang, Mingshi