The Role of Nuclear Factor-Kappa B in Fibrinogen-Induced Inflammatory Responses in Cultured Primary Neurons.
The Role of Nuclear Factor-Kappa B in Fibrinogen-Induced Inflammatory Responses in Cultured Primary Neurons.
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DOI：
10.3390/biom12121741
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发表时间：
2022-11-23
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
创伤性脑损伤是一种与血脑屏障(BBB)受损和神经变性相关的炎症性疾病。炎症的后果之一是血液中纤维蛋白原(Fg)水平升高，这是一种主要在肝脏产生的蛋白质。炎症引起的血脑屏障的变化导致FG外溢到脑实质，创造了它与神经元接触的可能性。我们之前已经证明，FG与神经元细胞间黏附分子-1和细胞Pron蛋白的相互作用诱导了促炎细胞因子的上调、氧化损伤、增加的细胞凋亡和细胞死亡。然而，参与这一过程的转录途径尚未确定。在原代培养的小鼠大脑皮层神经元上，研究了纤维蛋白原(FG)与核因子-κB(NF-κB)的激活以及由此产生的白细胞介素6(IL-6)和C-C趋化因子配体2(CCL2)的表达之间的关系。FG与神经元的特异性相互作用使FG诱导的CCL2、IL-6基因表达和NF-κB蛋白表达增加。这些结果提示，颅脑损伤所致的神经退变可能涉及渗出的FG与神经元的直接相互作用，通过激活转录因子NF-κB，导致促炎细胞因子的过度表达，这可能是神经炎症性疾病时血管认知功能障碍的机制之一。
Traumatic brain injury (TBI) is an inflammatory disease associated with a compromised blood–brain barrier (BBB) and neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg), a protein that is mainly produced in the liver. The inflammation-induced changes in the BBB result in Fg extravasation into the brain parenchyma, creating the possibility of its contact with neurons. We have previously shown that interactions of Fg with the neuronal intercellular adhesion molecule-1 and cellular prion protein induced the upregulation of pro-inflammatory cytokines, oxidative damage, increased apoptosis, and cell death. However, the transcription pathway involved in this process was not defined. The association of Fg with the activation of the nuclear factor-κB (NF-κB) and the resultant expression of interleukin-6 (IL-6) and C–C chemokine ligand-2 (CCL2) were studied in cultured primary mouse brain cortex neurons. Fg-induced gene expression of CCL2 and IL-6 and the expression of NF-κB protein were increased in response to a specific interaction of Fg with neurons. These data suggest that TBI-induced neurodegeneration can involve the direct interaction of extravasated Fg with neurons, resulting in the overexpression of pro-inflammatory cytokines through the activation of transcription factor NF-κB. This may be a mechanism involved in vascular cognitive impairment during neuroinflammatory diseases.
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影响因子：
2.9
作者：
Muradashvili N;Charkviani M;Sulimai N;Tyagi N;Crosby J;Lominadze D
通讯作者：
Lominadze D
影响因子：
8.3
作者：
del Zoppo GJ;Levy DE;Wasiewski WW;Pancioli AM;Demchuk AM;Trammel J;Demaerschalk BM;Kaste M;Albers GW;Ringelstein EB
通讯作者：
Ringelstein EB
影响因子：
2.5
作者：
Charkviani, Mariam;Muradashvili, Nino;Lominadze, David
通讯作者：
Lominadze, David
DOI：
10.1046/j.1365-2362.2002.00994.x
发表时间：
2002-05-01
影响因子：
5.5
作者：
Fiala, M;Liu, QN;Vinters, HV
通讯作者：
Vinters, HV
影响因子：
4
作者：
Muradashvili N;Tyagi R;Lominadze D
通讯作者：
Lominadze D