Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Dermatology, National Dermatology Center of Mongolia, Ulaanbaatar 14171, Mongolia.
Int J Mol Sci. 2019 Jul 6;20(13):3324. doi: 10.3390/ijms20133324.
The vicious itch-scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of in a scratch line number-dependent manner. Scratch-induced upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of and , even in the presence of IL-13. Scratch-induced expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling.
瘙痒-搔抓恶性循环是特应性皮炎（AD）的一个主要特征，其中 IL-13 信号发挥主导作用。角朊细胞表达两种受体：异二聚体 IL-4Rα/IL-13Rα1 和 IL-13Rα2。前者转导功能性 IL-13 信号，而后者 IL-13Rα2 作为无功能的诱饵受体发挥作用。为了研究搔抓损伤是否影响 IL-4Rα、IL-13Rα1 和 IL-13Rα2 的表达，我们用划痕损伤角质形成细胞单层，并用实时定量 PCR（qRT-PCR）和免疫荧光技术检测三种 IL-13 受体的表达。划痕损伤以划痕线数依赖性方式显著上调。在同时存在 IL-13 的情况下，划痕诱导的上调协同增强。相比之下，即使存在 IL-13，划痕损伤也不会改变和的表达。划痕诱导的表达依赖于 ERK1/2 和 p38 MAPK 信号。IL-13Rα2 蛋白的表达确实在划痕边缘区域增加，并且在苔藓样病变 AD 皮肤中也过表达。IL-13 抑制了表皮终末分化分子角蛋白的表达。在过表达 IL-13Rα2 的角质形成细胞中，IL-13 介导的角蛋白表达下调减弱，证实了 IL-13Rα2 的诱饵功能。我们的研究结果表明，搔抓可上调 IL-13 诱饵受体 IL-13Rα2 的表达并拮抗 IL-13 信号。
