TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation.
TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation.
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DOI：
10.1038/srep26088
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发表时间：
2016-05-18
影响因子：
4.6
通讯作者：
Miyata S
中科院分区：
文献类型：
--
作者：
Yoshida A;Furube E;Mannari T;Takayama Y;Kittaka H;Tominaga M;Miyata S
瞬时受体电位香草酸受体1（TRPV 1）是一种非选择性阳离子通道，其受热（>43 °C）、机械/渗透刺激和低pH刺激。TRPV 1在炎症反应中的重要性已被证明，而其在脑中的参与仍不清楚。在本研究中，侧脑室（icv）注射TRPV 1激动剂树脂毒素（RTX）诱导室周器官（CVO）和体温调节相关脑区信号转导和转录激活因子3（STAT 3）的激活，其模式与外周和icv注射脂多糖（LPS）相似。在外周和icv LPS刺激下，Trpv 1 −/−小鼠中的STAT 3活化显著低于Trpv 1 +/+小鼠。icv管理RTX诱导短暂的低温，而TRPV 1拮抗剂辣椒平增强LPS诱导的体温升高的幅度和时间。这些结果表明TRPV 1对于激活促炎性STAT 3信号传导和大脑中与体温调节相关的脑通路是重要的。
Transient receptor potential vanilloid receptor 1 (TRPV1) is a non-selective cation channel that is stimulated by heat (>43 °C), mechanical/osmotic stimuli, and low pH. The importance of TRPV1 in inflammatory responses has been demonstrated, whereas its participation in brains remains unclear. In the present study, the intracerebroventricular (icv) administration of the TRPV1 agonist resiniferatoxin (RTX) induced the activation of signal transducer and activator of transcription 3 (STAT3) in circumventricular organs (CVOs) and thermoregulation-associated brain regions with a similar patttern to the peripheral and icv administration of lipopolysaccharide (LPS). With the peripheral and icv LPS stimuli, STAT3 activation was significantly lower in Trpv1−/− mice than in Trpv1+/+ mice. The icv administration of RTX induced transient hypothermia, whereas that of the TRPV1 antagonist capsazepine enhanced the magnitude and period of LPS-induced hyperthermia. These results indicate that TRPV1 is important for activating proinflammatory STAT3 signaling and thermoregulation-associated brain pathways in the brain.