MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
School of Pharmacology and Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
Sci Rep. 2017 Mar 23;7:45155. doi: 10.1038/srep45155.
Transient Receptor Potential Melastatin-8 (TRPM8) reportedly plays a fundamental role in a variety of processes including cold sensation, thermoregulation, pain transduction and tumorigenesis. However, the role of TRPM8 in inflammation under cold conditions is not well known. Since cooling allows the convergence of primary injury and injury-induced inflammation, we hypothesized that the mechanism of the protective effects of cooling might be related to TRPM8. We therefore investigated the involvement of TRPM8 activation in the regulation of inflammatory cytokines. The results showed that TRPM8 expression in the mouse hypothalamus was upregulated when the ambient temperature decreased; simultaneously, tumor necrosis factor-alpha (TNFα) was downregulated. The inhibitory effect of TRPM8 on TNFα was mediated by nuclear factor kappa B (NFκB). Specifically, cold stress stimulated the expression of TRPM8, which promoted the interaction of TRPM8 and NFκB, thereby suppressing NFκB nuclear localization. This suppression consequently led to the inhibition of TNFα gene transcription. The present data suggest a possible theoretical foundation for the anti-inflammatory role of TRPM8 activation, providing an experimental basis that could contribute to the advancement of cooling therapy for trauma patients.
瞬时受体电位 M 型 8（TRPM8）据报道在多种过程中发挥着基本作用，包括冷感觉、体温调节、疼痛转导和肿瘤发生。然而，TRPM8 在冷条件下炎症中的作用尚不清楚。由于冷却允许初级损伤和损伤诱导的炎症汇聚，我们假设冷却的保护作用机制可能与 TRPM8 有关。因此，我们研究了 TRPM8 激活在调节炎症细胞因子中的作用。结果表明，当环境温度降低时，小鼠下丘脑的 TRPM8 表达上调；同时，肿瘤坏死因子-α（TNFα）下调。TRPM8 对 TNFα 的抑制作用是通过核因子 κB（NFκB）介导的。具体来说，冷应激刺激 TRPM8 的表达，促进 TRPM8 和 NFκB 的相互作用，从而抑制 NFκB 核定位。这种抑制作用继而导致 TNFα 基因转录的抑制。本数据为 TRPM8 激活的抗炎作用提供了一个可能的理论基础，为创伤患者的冷却治疗提供了实验依据。
