Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Pharmacol Rep. 2018 Apr;70(2):251-257. doi: 10.1016/j.pharep.2017.10.001. Epub 2017 Oct 5.
Atopic dermatitis is a chronic and severe pruritic skin disease. Interlukin-31 (IL-31) has been recently demonstrated to be one of the key pruritogens in atopic dermatitis. However, the mechanisms underlying IL-31-induced itching remains unclear. In our previous study, we have shown that thromboxane (TX) A is involved in itch-associated responses in mice with atopy-like skin diseases.
IL-31 was given intradermally into the rostral back of ICR mice and the hind-paw scratching to the injection site were counted. Expression of TX synthase and IL-31 receptors were analyzed using immunohistochemical staining or RT-PCR in mouse skin or primary cultures of mouse keratinocytes. The concentration of TXB, a metabolite of TXA, in the skin and the culture medium of primary cultures of mouse keratinocytes was measured using enzyme immunoassay. The concentration of intracellular Ca ions in mouse keratinocytes was measured using the calcium imaging method.
An intradermal injection of IL-31 elicited scratching, an itch-related response, in mice. The scratching was inhibited by TP TXA receptor antagonist DCHCH. The distribution of TX synthase and IL-31RA receptor was mainly epidermal keratinocytes in the skin. The primary cultures of keratinocytes expressed the mRNAs of TX synthase and IL-31 receptors. IL-31 increased the concentration of TXB, which was inhibited by TX synthase inhibitor sodium ozagrel and EGTA, in the skin and the culture medium of primary cultures of keratinocytes. IL-31 increased the concentration of intracellular Ca ions in mouse keratinocytes.
It is suggested that IL-31 elicits itch-associated responses through TXA produced from keratinocytes.
特应性皮炎是一种慢性且严重的瘙痒性皮肤病。白细胞介素-31（IL-31）最近被证明是特应性皮炎的主要瘙痒原之一。然而，IL-31 诱导瘙痒的机制尚不清楚。在我们之前的研究中，我们已经表明血栓素（TX）A 参与了特应性皮炎样皮肤病小鼠的瘙痒相关反应。
将 IL-31 皮内注射到 ICR 小鼠的头背部，计算注射部位的后爪搔抓次数。使用免疫组织化学染色或 RT-PCR 分析 TX 合酶和 IL-31 受体在小鼠皮肤或原代培养的小鼠角质形成细胞中的表达。使用酶免疫测定法测量皮肤和原代培养的小鼠角质形成细胞培养基中 TXB（TXA 的代谢产物）的浓度。使用钙成像方法测量小鼠角质形成细胞内 Ca 离子的浓度。
IL-31 皮内注射可诱发小鼠搔抓，即瘙痒相关反应。TP TXA 受体拮抗剂 DCHCH 抑制搔抓。TX 合酶和 IL-31RA 受体的分布主要在皮肤的表皮角质形成细胞中。角质形成细胞原代培养物表达 TX 合酶和 IL-31 受体的 mRNAs。IL-31 增加了 TXB 的浓度，TX 合酶抑制剂钠奥扎格雷和 EGTA 可抑制皮肤和角质形成细胞原代培养物培养基中的 TXB 浓度。IL-31 增加了小鼠角质形成细胞内 Ca 离子的浓度。
提示 IL-31 通过角质形成细胞产生的 TXA 引发瘙痒相关反应。
