Synergistic interactions between cytokines and AVP at the blood-CSF barrier result in increased chemokine production and augmented influx of leukocytes after brain injury.
Synergistic interactions between cytokines and AVP at the blood-CSF barrier result in increased chemokine production and augmented influx of leukocytes after brain injury.
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DOI：
10.1371/journal.pone.0079328
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chodobski A
中科院分区：
文献类型：
--
作者：
Szmydynger-Chodobska J;Gandy JR;Varone A;Shan R;Chodobski A
几条证据表明，血-脑脊液屏障（BCSFB），主要存在于脉络丛（CP），不仅在神经炎性疾病，如多发性硬化症，而且在创伤性脑损伤（TBI）中起着重要的病理生理作用。在这里，我们研究了精氨酸加压素（AVP）如何在创伤后神经炎症的背景下调节BCSFB的功能。以前已经表明，AVP加剧了各种形式的脑损伤，但这种AVP作用的机制知之甚少。1A型AVP受体在CP上皮细胞上高度表达，CP合成AVP。使用控制皮质撞击模型TBI，我们证明了减少创伤后产生的促炎介质的CP和减少流入的炎症细胞在AVP缺陷的Brattleboro大鼠的BCSFB相比，长埃文斯大鼠，Brattleboro大鼠的亲本品系。精氨酸加压素也被发现在创伤后激活的c-Jun N-末端激酶（JNK）在CP中发挥重要作用。在CP上皮细胞培养物中，AVP增强了促炎介质（包括中性粒细胞趋化因子）合成的肿瘤坏死因子-α和白细胞介素-1 β依赖性增加，这一作用在很大程度上依赖于JNK信号通路。在体内条件下，选择性JNK抑制剂减少创伤后产生的中性粒细胞化学引诱物的CP和减少流入的中性粒细胞通过BCSFB。这些结果为促炎细胞因子和AVP（G蛋白偶联受体的配体）之间的协同相互作用提供了证据，并支持AVP在创伤后神经炎症中的病理生理作用。
Several lines of evidence indicate that the blood-cerebrospinal fluid barrier (BCSFB), which primarily resides in the choroid plexus (CP), plays a significant pathophysiological role not only in neuroinflammatory diseases, such as multiple sclerosis, but also in traumatic brain injury (TBI). Here we investigated how arginine vasopressin (AVP) regulates function of the BCSFB in the context of post-traumatic neuroinflammation. It has previously been shown that AVP exacerbates various forms of brain injury, but the mechanisms underlying this AVP action are poorly understood. Type 1A AVP receptor is highly expressed on the CP epithelium and the CP synthesizes AVP. Using the controlled cortical impact model of TBI, we demonstrated decreased post-traumatic production of proinflammatory mediators by the CP and reduced influx of inflammatory cells across the BCSFB in AVP-deficient Brattleboro rats when compared with Long-Evans rats, a parental strain for Brattleboro rats. Arginine vasopressin was also found to play an important role in post-traumatic activation of c-Jun N-terminal kinase (JNK) in the CP. In the CP epithelial cell cultures, AVP augmented the tumor necrosis factor-α– and interleukin-1β–dependent increase in synthesis of proinflammatory mediators, including neutrophil chemoattractants, an action largely dependent on the JNK signaling pathway. Under in vivo conditions, a selective JNK inhibitor decreased the post-traumatic production of neutrophil chemoattractants by the CP and reduced the influx of neutrophils across the BCSFB. These results provide evidence for the synergistic interactions between proinflammatory cytokines and AVP, a ligand for G protein-coupled receptors, and support a pathophysiological role of AVP in post-traumatic neuroinflammation.
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影响因子：
30.5
作者：
Reboldi, Andrea;Coisne, Caroline;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
2.9
作者：
Zheng, W;Zhao, QQ
通讯作者：
Zhao, QQ
影响因子：
4.2
作者：
Trabold, Raimund;Krieg, Sandro;Plesnila, Nikolaus
通讯作者：
Plesnila, Nikolaus
DOI：
10.1093/jnen/59.7.561
发表时间：
2000-07-01
影响因子：
3.2
作者：
Strazielle, N;Ghersi-Egea, JF
通讯作者：
Ghersi-Egea, JF
影响因子：
2.9
作者：
Utagawa, Akira;Bramlett, Helen M.;Dietrich, W. Dalton
通讯作者：
Dietrich, W. Dalton