Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1
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DOI：
10.3390/jcm9030891
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发表时间：
2020-03
影响因子：
3.9
通讯作者：
G. Tsuji;A. Hashimoto-Hachiya;V. H. Yen;Sho Miake;M. Takemura;Y. Mitamura;Takamichi Ito;Maho Murata;M. Furue;T. Nakahara
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文献类型：
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作者：
G. Tsuji;A. Hashimoto-Hachiya;V. H. Yen;Sho Miake;M. Takemura;Y. Mitamura;Takamichi Ito;Maho Murata;M. Furue;T. Nakahara
背景：IL-33 是 IL-1 超家族细胞因子之一，已被证明与特应性皮炎 (AD) 的瘙痒和炎症有关。此外，据报道，角质形成细胞产生的 IL-33 在 AD 的发展中起着至关重要的作用。然而，IL-33表达的机制尚未完全清楚。方法：我们分析了用 IL-4 处理的正常人表皮角质形成细胞 (NHEK) 中 IL-33 的表达。结果：IL-4 诱导 NHEK 中 IL-33 表达上调。基于以下发现：1) AD 易感基因 ovo-like 1 (OVOL1) 上调 NHEK 中丝聚蛋白 (FLG) 和兜甲素 (LOR) 的表达，2) 减少 FLG 和 LOR 的表达导致 IL-1 超家族细胞因子的产生，我们检查了 OVOL1 与 NHEK 中 IL-33 表达的关系。 OVOL1 的敲低诱导 IL-33 表达上调。此外，据报道，芳基烃受体 (AHR) 激活剂 Glyteer 会上调 OVOL1 表达，因此我们检查了 Glyteer 治疗是否会抑制 NHEK 中的 IL-33 表达。 Glyteer 治疗可抑制 IL-4 诱导的 IL-33 表达上调，而这种上调可通过敲低 AHR 或 OVOL1 来取消。结论：AHR-OVOL1轴的激活抑制IL-4诱导的IL-33表达，可能有利于AD的治疗。
Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. Methods: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. Results: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. Conclusions: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD.