在大鼠弥漫性轴索损伤后，巨噬细胞移动抑制因子的抑制通过 Toll 样受体相关通路来保护炎症反应。

Inhibition of Macrophage Migration Inhibitory Factor Protects against Inflammation through a Toll-like Receptor-Related Pathway after Diffuse Axonal Injury in Rats.

机构信息

Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Department of Gynecology and Obstetrics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Biomed Res Int. 2020 Sep 5;2020:5946205. doi: 10.1155/2020/5946205. eCollection 2020.

OBJECTIVE

We have previously demonstrated that inflammation induced by toll-like receptors (TLRs) 2/4 exert cerebral deleterious effects after diffuse axonal injury (DAI); however, the underlying mechanisms are not fully understood. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in inflammatory responses. The purpose of this study was to investigate the role of MIF in inflammation induced by TLRs in the cortices of DAI rats.

METHODS

The rat DAI model was established by head rotational acceleration and confirmed by -APP, HE, and silver staining. MIF protein expression at 3 h, 6 h, 12 h, 1 d, and 3 d after DAI was measured by western blot. The localization of MIF was measured by immunofluorescence. MIF antagonist ISO-1 was intracerebroventricularly injected to inhibit MIF. Neuronal and axonal injury and glial responses were assessed by TUNEL, immunohistochemistry, and TEM. Expression of TLR2, TLR4, ERK, phospho-ERK, NF-B, and phospho-NF-B was examined by western blot. The level of IL-1, IL-6, and TNF- was measured by ELISA.

RESULTS

MIF expression was significantly increased, peaking at 1 day after DAI, and MIF was mainly localized in microglial cells and neurons. ISO-1 suppressed neuronal apoptosis, axonal injury, and glial responses and decreased the expression of downstream signaling molecules related to TLR2/4, including ERK, phospho-ERK, NF-B, phospho-NF-B, IL-1, IL-6, and TNF-.

CONCLUSION

MIF was involved in the neuronal and axonal damage through a TLR-related pathway following DAI.

目的

我们之前已经证明， Toll 样受体（TLRs）2/4 引起的炎症在弥漫性轴索损伤（DAI）后对大脑产生有害影响；然而，其潜在机制尚不完全清楚。巨噬细胞移动抑制因子（MIF）是一种参与炎症反应的多功能细胞因子。本研究旨在探讨 MIF 在 DAI 大鼠皮质 TLR 诱导的炎症中的作用。

方法

通过头部旋转加速建立大鼠 DAI 模型，并通过β-淀粉样蛋白前体（APP）、苏木精和伊红（HE）以及银染色进行验证。通过 Western blot 测量 DAI 后 3 h、6 h、12 h、1 d 和 3 d 时 MIF 蛋白的表达。通过免疫荧光测量 MIF 的定位。通过脑室注射 MIF 拮抗剂 ISO-1 抑制 MIF。通过 TUNEL、免疫组织化学和 TEM 评估神经元和轴突损伤以及神经胶质反应。通过 Western blot 检测 TLR2、TLR4、ERK、磷酸化-ERK、NF-B 和磷酸化-NF-B 的表达。通过 ELISA 测量 IL-1、IL-6 和 TNF-α的水平。