Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2.
Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2.
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DOI：
10.1523/jneurosci.5741-07.2008
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发表时间：
2008-12-17
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影响因子：
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通讯作者：
Caterina MJ
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文献类型：
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作者：
Huang SM;Lee H;Chung MK;Park U;Yu YY;Bradshaw HB;Coulombe PA;Walker JM;Caterina MJ
感知环境变化的能力对生存至关重要，因为它允许诸如从有害刺激中撤退和调节体温等反应。角质形成细胞占据皮肤表皮的大部分，位于外部环境和身体内部环境之间的界面，并且长期以来一直因其抵抗外部侵害的屏障功能而受到重视。最近在角质形成细胞中发现了温度敏感性TRPV离子通道，这提高了这些细胞也积极参与急性温度和疼痛感觉的可能性。为了解决这一问题，我们产生并表征了在角蛋白14启动子控制下在表皮角质形成细胞中过表达TRPV 3的转基因小鼠。与野生型对照组相比，过度表达TRPV 3的角质形成细胞对两种TRPV 3激动剂，2-氨基乙氧基二苯基硼酸酯（2APB）和热的反应表现出更大的电流以及增加的前列腺素E2（PGE 2）释放。过表达TRPV 3的未处理小鼠的热选择行为和热诱发的戒断行为没有一致的改变。然而，在使用JNJ-7203212选择性药理学抑制TRPV 1后，角质形成细胞特异性TRPV 3转基因小鼠显示，相对于其野生型同窝小鼠，对有害热的逃避反应增加。共同管理的环氧合酶抑制剂，布洛芬，与TRPV 1拮抗剂减少炎性热痛觉过敏的转基因动物，但不是野生型。我们的研究结果揭示了一个以前未描述的机制，角质形成细胞参与热疼痛转导通过角质形成细胞TRPV 3离子通道和细胞间信使PGE 2。
The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much of the skin epidermis, are situated at the interface between the external environment and the body's internal milieu, and have long been appreciated for their barrier function against external insults. The recent discovery of temperature-sensitive TRPV ion channels in keratinocytes has raised the possibility that these cells also actively participate in acute temperature and pain sensation. To address this notion, we generated and characterized transgenic mice that overexpress TRPV3 in epidermal keratinocytes under the control of the keratin 14 promoter. Compared to wild-type controls, keratinocytes overexpressing TRPV3 exhibited larger currents as well as augmented prostaglandin E2 (PGE2) release in response to two TRPV3 agonists, 2-aminoethoxydiphenyl borate (2APB) and heat. Thermal selection behavior and heat-evoked withdrawal behavior of naïve mice overexpressing TRPV3 were not consistently altered. Upon selective pharmacological inhibition of TRPV1 with JNJ-7203212, however, the keratinocyte-specific TRPV3 transgenic mice showed increased escape responses to noxious heat relative to their wild-type littermates. Co-administration of the cyclooxygenase inhibitor, ibuprofen, with the TRPV1 antagonist decreased inflammatory thermal hyperalgesia in transgenic but not wild-type animals. Our results reveal a previously undescribed mechanism for keratinocyte participation in thermal pain transduction through keratinocyte TRPV3 ion channels and the intercellular messenger PGE2.