Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Department of Immunobiology, Federal Fluminense University, Niterói, Brazil.
Scand J Immunol. 2023 Apr;97(4):e13258. doi: 10.1111/sji.13258. Epub 2023 Feb 13.
The relationship between psoriasis severity and psychological stress has been described in several studies. However, the mechanism by which chronic stress exacerbates psoriasis is not completely understood. This study aimed at investigating whether chronic psychological stress can aggravate psoriasis-like skin inflammation. Mice were subjected to a restraint stress model and topically treated with imiquimod (IMQ). Differentiated human keratinocytes were treated with high epinephrine levels and IMQ in vitro. Stress aggravated macroscopic features and the increase in epidermal thickness induced by IMQ in mouse skin. The increase in NF-κB and IL-17A expression induced by IMQ was potentiated by chronic stress in mouse skin. The skin of stressed mice treated with IMQ showed higher levels of β-adrenergic receptors (β-AR). In human keratinocytes, high epinephrine levels exacerbated the increase in the levels of β-AR and IL-17A induced by IMQ. β-AR antagonist reversed the effects of chronic stress in IMQ-induced inflammation both in vivo and in vitro. In conclusion, stress-stimulated overactivation of the β-AR and NF-κB pathways potentiates a Th1/Th17 profile leading to an exacerbation of psoriasis.
几项研究描述了银屑病严重程度与心理压力之间的关系。然而，慢性应激加重银屑病的机制尚不完全清楚。本研究旨在探讨慢性心理应激是否会加重银屑病样皮肤炎症。将小鼠置于束缚应激模型中，并局部用咪喹莫特（IMQ）处理。体外将分化的人角质形成细胞用高肾上腺素水平和 IMQ 处理。应激加重了 IMQ 诱导的小鼠皮肤宏观特征和表皮厚度增加。慢性应激增强了 IMQ 诱导的 NF-κB 和 IL-17A 表达的增加。用 IMQ 处理的应激小鼠的皮肤显示出更高水平的β-肾上腺素能受体（β-AR）。在人角质形成细胞中，高肾上腺素水平加剧了 IMQ 诱导的β-AR 和 IL-17A 水平的增加。β-AR 拮抗剂在体内和体外均逆转了 IMQ 诱导的炎症中慢性应激的作用。总之，应激刺激的β-AR 和 NF-κB 途径过度激活增强了 Th1/Th17 表型，导致银屑病加重。
