Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by suppressing the NF-kappa B signaling pathway
Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by suppressing the NF-kappa B signaling pathway
复制标题
Tim-4 通过抑制 NF-kappa B 信号通路保护小鼠免受脂多糖诱导的内毒素休克
DOI：
10.1038/labinvest.2016.94
复制
发表时间：
2016
影响因子：
5
通讯作者：
Gao Lifen
中科院分区：
文献类型：
--
作者：
Xu Liyun;Zhao Peiqing;Xu Yong;Gao Lishuang;Wang Hongxing;Jia Xiaoxia;Ma Hongxin;Liang Xiaoxong;Ma Chunxong;Gao Lifen
内毒素休克是医院患者发病和死亡的主要原因，迫切需要探讨脓毒症的发病机制。我们以前的研究表明，T细胞免疫球蛋白和粘蛋白结构域包含分子-4(TIM-4)通过调节巨噬细胞的功能来减轻炎症反应。然而，TIM-4起作用的机制还没有完全阐明。在本研究中，我们发现内毒素休克时TIM-4表达增加。有趣的是，脂多糖注射后，TIM-4高表达组小鼠的存活率高于对照组。为了探讨TIM-4在内毒素诱导的炎症反应中的作用，我们进一步证实了TIM-4通过抑制巨噬细胞产生细胞因子来减轻内毒素休克。阻断TIM-4的表达和核转录因子-kappaB(NF-κB)信号的抑制，表明TIM-4通过核因子-κB信号通路抑制细胞因子的产生。本研究表明，TIM-4可能通过调节炎症因子的分泌而发挥免疫调节作用，可能成为治疗炎症性疾病特别是内毒素休克的新靶点。
Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin-and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.