Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes
Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes
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DOI：
10.1124/jpet.102.040675
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发表时间：
2003-01-01
影响因子：
3.5
通讯作者：
Travers, JB
中科院分区：
文献类型：
--
作者：
Southall, MD;Li, T;Travers, JB
在皮肤损伤和相关的创伤期间，释放出许多可以介导炎症反应的化合物。确定启动急性角质形成细胞损伤的炎症反应的细胞机制对于理解表皮炎症的调节是重要的。最近克隆的香草素受体-1（VR 1）是一种多模式受体，对热、pH或辣椒素等香草素刺激有反应。尽管VR 1仅定位于感觉神经元和中枢神经系统内，但最近的证据表明功能性VR 1在人类皮肤和表皮细胞中表达。使用逆转录-聚合酶链反应和免疫印迹，我们报告说，人角质形成细胞和人角质形成细胞系HaCaT表达VR 1。与神经元VR 1一致，辣椒素激活表皮VR 1诱导钙内流。用辣椒素处理HaCaT细胞导致环氧合酶-2（考克斯-2）的剂量依赖性表达，而用VR 1受体拮抗剂辣椒平预处理消除辣椒素刺激的考克斯-2表达的增加。辣椒素诱导的考克斯-2表达依赖于细胞外钙离子。辣椒素激活表皮VR 1也导致白细胞介素-8和前列腺素E-2的释放增加，刺激释放被辣椒平减弱。VR 1由角质形成细胞表达的发现非常重要，因为它扩展了VR 1的假定作用，超出了疼痛感知的范围。我们的研究结果表明，VR 1在角质形成细胞中的表达可能在继发于表皮损伤或损伤的炎症中发挥作用，因此可能作为有害皮肤刺激的传感器发挥作用。
During dermal injury and the associated trauma a number of compounds are released that can mediate the inflammatory response. Determining the cellular mechanisms that initiate the inflammatory responses to acute keratinocyte damage is important for understanding the regulation of epidermal inflammation. The recently cloned vanilloid receptor-1 (VR1) is a polymodal receptor, responding to thermal, pH, or vanilloids such as capsaicin stimulation. Although VR1 has been localized only on sensory neurons and within the central nervous system, recent evidence suggests a functional VR1 is expressed in human skin and epidermal cells. Using reverse transcription-polymerase chain reaction and immunoblotting we report that human keratinocytes and the human keratinocyte cell line HaCaT express VR1. Consistent with neuronal VR1, activation of epidermal VR1 by capsaicin induced a calcium influx. Treating HaCaT cells with capsaicin resulted in a dose-dependent expression of cyclooxygenase-2 (COX-2), whereas pretreatment with the VR1 receptor antagonist capsazepine abolished the capsaicin-stimulated increase in COX-2 expression. Furthermore, the capsaicin-induced expression of COX-2 was dependent on extracellular calcium. Activation of the epidermal VR1 by capsaicin also resulted in an increased release of interleukin-8 and prostaglandin E-2, and the stimulated release was attenuated by capsazepine. The finding that VR1 is expressed by keratinocytes is of great importance because it expands the putative role of VR1 beyond that of pain perception. Our results suggest that VR1 expression in keratinocytes may have a role in the inflammation that occurs secondary to epidermal damage or insult, and thus may function as a sensor for noxious cutaneous stimulation.