Department of Dermatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.
Int J Mol Sci. 2023 Jul 5;24(13):11104. doi: 10.3390/ijms241311104.
While atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, an increase in other types of inflammatory cytokines is also noted in AD and they may also contribute to the development of the disease. Recently, the efficacy of an anti-IL-36 receptor antibody in AD was demonstrated in a clinical trial. Although there have been several reports on IL-36α and IL-36γ expression and function in AD, IL-36β has been barely studied. In this report, we examined IL-36β expression and function using clinical samples of AD and the epidermal keratinocyte cell line, HaCaT cells. We demonstrated that IL-36β expression in epidermal keratinocytes was increased in AD lesional skin compared to healthy skin. IL-36β promoted vascular endothelial growth factor A production in HaCaT keratinocytes through phosphorylation of extracellular signal-regulated kinases 1 and 2. In addition, IL-36β up-regulated placental growth factor mRNA expression in HaCaT keratinocytes. IL-36β expression levels in epidermal keratinocytes were correlated with the number of dermal vessels in AD skin. These results suggest that IL-36β may play an important role for angiogenesis in lesional skin of AD and that IL-36β can be a therapeutic target in AD.
虽然特应性皮炎（AD）被认为是一种以辅助性 T 细胞 2（Th2）为中心的疾病，但在 AD 中也注意到其他类型的炎症细胞因子增加，它们也可能有助于疾病的发展。最近，一项临床试验证明了抗白细胞介素-36 受体抗体在 AD 中的疗效。尽管已经有关于 AD 中白细胞介素-36α 和白细胞介素-36γ 的表达和功能的几个报告，但白细胞介素-36β 几乎没有被研究过。在本报告中，我们使用 AD 的临床样本和表皮角质形成细胞系 HaCaT 细胞检查了白细胞介素-36β 的表达和功能。我们证明，与健康皮肤相比，AD 病变皮肤中表皮角质形成细胞中的白细胞介素-36β 表达增加。白细胞介素-36β 通过磷酸化细胞外信号调节激酶 1 和 2 促进 HaCaT 角质形成细胞中血管内皮生长因子 A 的产生。此外，白细胞介素-36β 在 HaCaT 角质形成细胞中上调胎盘生长因子 mRNA 的表达。表皮角质形成细胞中的白细胞介素-36β 表达水平与 AD 皮肤中真皮血管的数量相关。这些结果表明白细胞介素-36β 可能在 AD 病变皮肤的血管生成中发挥重要作用，并且白细胞介素-36β 可以成为 AD 的治疗靶点。
