Pavlenko Darya, Funahashi Hideki, Sakai Kent, Hashimoto Takashi, Lozada Taisa, Yosipovitch Gil, Akiyama Tasuku
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Psychiatry, University of Miyazaki, Kiyotake, Japan.
Exp Dermatol. 2020 Dec;29(12):1209-1215. doi: 10.1111/exd.14206. Epub 2020 Oct 19.
Accumulating evidence has highlighted the essential roles of cytokines in itch processing. Although IL-23 and Th17 cytokines are elevated in inflammatory skin disorders, their role in itch is unknown. Here, we investigated the role of IL-23 and IL-17A in itch response using an in vitro calcium imaging of mouse dorsal root ganglion (DRG) neurons and an in vivo behaviour test. Calcium imaging studies revealed that a few DRG neurons (~5%) responded to either IL-23 or IL-17A. Pretreatment cells with IL-23 significantly reduced calcium responses to histamine and capsaicin but not chloroquine. Behaviour experiments showed neither IL-23 nor IL-17A evoked scratching. IL-23 significantly decreased histamine-evoked scratching without affecting chloroquine-evoked scratching. There was no difference in scratching between IL-17A- and vehicle-treated groups. These results indicate that IL-23 might play a role in regulating histaminergic itch via modulation of TRPV1 activity.
越来越多的证据表明细胞因子在瘙痒传导过程中起重要作用。虽然白细胞介素-23(IL-23)和辅助性T细胞17(Th17)细胞因子在炎症性皮肤病中水平升高,但其在瘙痒中的作用尚不清楚。在此,我们使用小鼠背根神经节(DRG)神经元的体外钙成像和体内行为测试,研究了IL-23和白细胞介素-17A(IL-17A)在瘙痒反应中的作用。钙成像研究显示,少数DRG神经元(约5%)对IL-23或IL-17A有反应。用IL-23预处理细胞可显著降低对组胺和辣椒素的钙反应,但对氯喹无此作用。行为实验表明,IL-23和IL-17A均未诱发抓挠。IL-23显著减少组胺诱发的抓挠,而不影响氯喹诱发的抓挠。IL-17A处理组和溶剂处理组之间的抓挠无差异。这些结果表明,IL-23可能通过调节瞬时受体电位香草酸亚型1(TRPV)1活性在调节组胺能性瘙痒中发挥作用。