Molecular elucidation and medical significance of redox-sensitive TRP channels in inflammatory cell infiltration.

活性氧（ROS）诱导趋化因子，负责在损伤或感染的炎症部位募集炎性细胞。在这里，我们证明了质膜Ca^2渗透通道TRPM2控制ROS诱导的单核细胞趋化因子的产生。TRPM 2 Ca^2内流控制ROS诱导的信号级联反应，负责趋化因子的产生，从而加剧炎症。另一方面，严格控制氧气（O_2）的摄入量，以确保能量的产生，同时最大限度地减少有氧生物体中氧化损伤的风险。哺乳动物的呼吸系统已经进化到通过颈动脉体和其他化学感受器对O_2可用性的变化做出反应。在这里，我们的TRP阳离子通道在小鼠迷走神经化学感受器中表达的功能检查表明，TRPA1通道被激活的O2和介导的离子电流高氧通过其突出的敏感性半胱氨酸介导的氧化。TRPA1在缺氧时也被脯氨酰羟化酶激活，解除O_2依赖性抑制。高氧和低氧诱导的迷走神经传入神经活动及其随后的兴奋反应由TRPA 1控制。因此，TRPA 1是一种调节体内O_2供应的O_2传感器。

Reactive oxygen species(ROS) induce chemokines responsible for the recruitment of inflammatory cells at inflamed sites in injury or infection. Here, we demonstrate that the plasma membrane Ca^2-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. TRPM2 Ca^2 influx controls the ROS-induced signal cascade responsible for chemokine production which aggravates inflammation. On the other hand, Oxygen(O_2) intake is tightly controlled in order to secure energy production while minimizing the risk of oxidative damage in aerobic organisms. Mammals' respiratory systems have evolved to respond to changes in O_2 availability via the carotid body and other chemoreceptors. Here, our functional examination of the TRP cation channels expressed in mouse vagal chemoreceptors reveals that the TRPA1 channel is activated by O2 and mediates ionic currents in hyperoxia via its prominent sensitivity to cysteine-mediated oxidation. TRPA1 is also activated in hypoxia through relief from O_2-dependent inhibition by prolyl hydroxylases. Hyperoxia-and hypoxia-induced vagal afferent nerve activities and their consequent ventilatory responses are are controlled by TRPA1. Thus, TRPA1 is an O_2 sensor that regulates O_2supply in vivo.