Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-1094, Japan.
Acta Derm Venereol. 2017 Aug 31;97(8):922-927. doi: 10.2340/00015555-2697.
A recent study suggests that interleukin-31 (IL-31) exerts its effect via indirect mechanisms rather than through direct stimulation of cutaneous nerves. However, the underlying peripheral mechanisms of IL-31-induced itch in the skin remain unclear. Therefore, the present study investigated the peripheral mechanisms underlying IL-31-induced itch in mice. IL-31-induced itch-related response was inhibited by anti-allergic drugs (tranilast and azelastine), but not by an H1 histamine receptor antagonist (terfenadine). Furthermore, a 5-lipoxygenase inhibitor (zileuton), but not a cyclooxygenase inhibitor (indomethacin), and a leuko-triene B4 (LTB4) receptor antagonist (CMHVA) attenuated the action of IL-31. IL-31 receptor-immunoreactivity was observed in the epidermis and primary sensory neurones. IL-31 receptor mRNA was expressed in mouse keratinocytes and dorsal root ganglia neurones. IL-31 increased the production of LTB4 in mouse keratinocytes. These results suggest that IL-31 elicits itch not only through direct action on primary sensory neurones, but also by inducing LTB4 production in keratinocytes.
最近的一项研究表明，白细胞介素-31（IL-31）通过间接机制发挥作用，而不是通过直接刺激皮肤神经。然而，IL-31 诱导皮肤瘙痒的外周机制尚不清楚。因此，本研究探讨了 IL-31 诱导小鼠瘙痒的外周机制。IL-31 诱导的瘙痒相关反应被抗过敏药物（曲尼司特和氮卓斯汀）抑制，但被 H1 组胺受体拮抗剂（特非那定）抑制。此外，5-脂氧合酶抑制剂（齐留通），而不是环氧化酶抑制剂（吲哚美辛）和白三烯 B4（LTB4）受体拮抗剂（CMHVA）减弱了 IL-31 的作用。在表皮和初级感觉神经元中观察到 IL-31 受体免疫反应性。IL-31 受体 mRNA 在小鼠角质形成细胞和背根神经节神经元中表达。IL-31 增加了小鼠角质形成细胞中 LTB4 的产生。这些结果表明，IL-31 不仅通过直接作用于初级感觉神经元引起瘙痒，还通过诱导角质形成细胞中 LTB4 的产生引起瘙痒。
