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

活性氧（ROS）诱导的趋化因子负责在损伤或感染的炎症部位招募炎症细胞。在这里，我们证明了质膜ca2 -通透通道TRPM2控制ros诱导的单核细胞趋化因子的产生。TRPM2 Ca^2内流控制ros诱导的信号级联，负责趋化因子的产生，从而加重炎症。另一方面，氧气（O_2）的摄入是严格控制的，以确保能量的产生，同时最大限度地降低有氧生物氧化损伤的风险。哺乳动物的呼吸系统已经进化到可以通过颈动脉体和其他化学感受器对氧气供应的变化做出反应。在这里，我们对小鼠迷走神经化学感受器中表达的TRP阳离子通道的功能检查表明，TRPA1通道被O2激活，并通过其对半胱氨酸介导的氧化的突出敏感性介导高氧离子电流。TRPA1也在缺氧时通过解除脯氨酸羟化酶对o_2依赖性的抑制而被激活。高氧和低氧诱导的迷走神经传入神经活动及其随后的通气反应是由TRPA1控制的。因此，TRPA1是调节体内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.