TNFα Triggers an Augmented Inflammatory Response in Brain Neurons from Dahl Salt-Sensitive Rats Compared with Normal Sprague Dawley Rats.
TNFα Triggers an Augmented Inflammatory Response in Brain Neurons from Dahl Salt-Sensitive Rats Compared with Normal Sprague Dawley Rats.
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DOI：
10.1007/s10571-021-01056-9
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发表时间：
2022-08
影响因子：
4
通讯作者：
Shan Z
中科院分区：
文献类型：
--
作者：
Gao H;Bigalke J;Jiang E;Fan Y;Chen B;Chen QH;Shan Z
肿瘤坏死因子(TNF)-α是一种促炎细胞因子（PIC），与包括心血管疾病在内的多种疾病有关。本研究研究了TNFα在Sprague Dawley （SD）大鼠培养的脑神经元和下丘脑室旁核（PVN）（与心血管相关的关键脑区）中引发的炎症反应。我们的研究结果表明，TNFα治疗可诱导包括白细胞介素(IL)-1β和白细胞介素-6 （IL6）在内的PICs mRNA表达的剂量和时间依赖性增加；C-C Motif趋化因子配体5 （CCL5）和C-C Motif趋化因子配体12 （CCL12）、诱导型一氧化氮合酶（iNOS）和转录因子NF-kB在培养的新生SD大鼠脑神经元中的表达。与此发现一致的是，免疫染色显示TNFα处理增加了成年SD大鼠培养的脑神经元和PVN中il - 1β、CCL5、iNOS的免疫反应性，并刺激NF-kB的激活或表达。我们进一步比较了上述基因在SD大鼠和Dahl盐敏感（Dahl- s）大鼠（盐敏感性高血压动物模型）基础水平的mRNA表达以及对TNFα攻击的响应。Dahl-S脑神经元CCL5、iNOS和il - 1β mRNA表达的基线水平更高，对tnf - α刺激的反应也更大。此外，中枢给药TNFα可显著提高Dahl S大鼠PVN中CCL12的应答。在Dahl-S大鼠模型中，对tnf - α的炎症反应增加可能表明了一种潜在的机制，即在Dahl-S大鼠模型中，血压对盐摄入的反应性增强。
Tumor Necrosis Factor (TNF)-α is a proinflammatory cytokine (PIC) and has been implicated in a variety of illness including cardiovascular disease. The current study investigated the inflammatory response trigged by TNFα in both cultured brain neurons and the hypothalamic paraventricular nucleus (PVN), a key cardiovascular relevant brain area, of the Sprague Dawley (SD) rats. Our results demonstrated that TNFα treatment induces a dose- and time-dependent increase in mRNA expression of PICs including Interleukin (IL)-1β and Interleukin-6 (IL6); chemokines including C-C Motif Chemokine Ligand 5 (CCL5) and C-C Motif Chemokine Ligand 12 (CCL12), inducible nitric oxide synthase (iNOS), as well as transcription factor NF-kB in cultured brain neurons from neonatal SD rats. Consistent with this finding, immunostaining shows that TNFα treatment increases immunoreactivity of IL1β, CCL5, iNOS and stimulates activation or expression of NF-kB, in both cultured brain neurons and the PVN of adult SD rats. We further compared mRNA expression of the aforementioned genes in basal level as well as in response to TNFα challenge between SD rats and Dahl Salt sensitive (Dahl-S) rats, an animal model of salt sensitive hypertension. Dahl-S brain neurons presented higher baseline levels as well as greater response to TNFα challenge in mRNA expression of CCL5, iNOS and IL1β. Furthermore, central administration of TNFα caused significant higher response in CCL12 in the PVN of Dahl S rats. The increased inflammatory response to TNFα in Dahl-S rats may be indicative of an underlying mechanism for enhanced pressor reactivity to salt intake in the Dahl-S rat model.
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DOI：
10.1111/apha.12963
发表时间：
2018-03
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Fan Y;Jiang E;Hahka T;Chen QH;Yan J;Shan Z
通讯作者：
Shan Z
脑核因子-κ B 激活有助于血管紧张素 II 诱导的高血压的神经体液兴奋
影响因子：
10.8
作者：
Kang, Yu-Ming;Ma, Ying;Francis, Joseph
通讯作者：
Francis, Joseph
影响因子：
2.7
作者：
Cottone, S;Vadala, A;Cerasola, G
通讯作者：
Cerasola, G
TNF在大脑中的抑制会逆转RAS成分的改变，并减弱血管紧张素II诱导的高血压。
影响因子：
3.7
作者：
Sriramula S;Cardinale JP;Francis J
通讯作者：
Francis J
DOI：
10.1152/ajpheart.00822.2016
发表时间：
2017-12-01
影响因子：
4.8
作者：
Huber, Michael J.;Fan, Yuanyuan;Shan, Zhiying
通讯作者：
Shan, Zhiying