Cho Kyung-Ah, Kim Hye Ji, Kim Yu-Hee, Park Minhwa, Woo So-Youn
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea,
Int Arch Allergy Immunol. 2019;179(1):53-61. doi: 10.1159/000494624. Epub 2019 Mar 25.
The skin is a dynamic body organ that can be activated by both central and local hypothalamic-pituitary-adrenal axis systems. This phenomenon might be the crucial explanation why stress can cause relapse of chronic inflammatory skin diseases, such as psoriasis. Here, we determined the effects of mast cells on keratinocyte proliferation under stress hormone stimulation.
We subcutaneously injected dexamethasone on the shaved back of mice and evaluated histological changes and keratinocyte growth factor (KGF) expression on dermal mast cells. Further, human mast cell line (HMC-1) and keratinocyte cell line (HaCaT) cells were treated with dexamethasone in vitro to observe the extent of proliferation and the expression of KGF. Finally, the supernatants of HMC-1 cells treated with dexamethasone were used for the culture of HaCaT cells to investigate the effect on proliferation.
We observed epidermal thickening in dexamethasone-injected mice, accompanied by an increase in the number of KGF-expressing dermal mast cells. Similar to mouse dermal mast cells, KGF was highly expressed in the human mast cell line HMC-1 following stimulation with dexamethasone. Further, dexamethasone-treated mast cells promoted keratinocyte proliferation in vitro. However, the effects of mast cells on keratinocytes were significantly diminished in the presence of anti-KGF-blocking antibodies.
Taken together, our results show that a stressful environment may disturb skin barrier homeostasis through mast cell-derived KGF expression.
皮肤是一个动态的身体器官,可被中枢和局部下丘脑 - 垂体 - 肾上腺轴系统激活。这种现象可能是压力导致慢性炎症性皮肤病(如银屑病)复发的关键解释。在此,我们确定了应激激素刺激下肥大细胞对角质形成细胞增殖的影响。
我们在小鼠剃毛的背部皮下注射地塞米松,并评估皮肤肥大细胞的组织学变化和角质形成细胞生长因子(KGF)表达。此外,在体外用地塞米松处理人肥大细胞系(HMC - 1)和角质形成细胞系(HaCaT)细胞,以观察增殖程度和KGF的表达。最后,用地塞米松处理的HMC - 1细胞的上清液用于培养HaCaT细胞,以研究对增殖的影响。
我们观察到注射地塞米松的小鼠表皮增厚,同时表达KGF的皮肤肥大细胞数量增加。与小鼠皮肤肥大细胞类似,地塞米松刺激后人肥大细胞系HMC - 1中KGF高度表达。此外,地塞米松处理的肥大细胞在体外促进角质形成细胞增殖。然而,在存在抗KGF阻断抗体的情况下,肥大细胞对角质形成细胞的作用显著减弱。
综上所述,我们的结果表明,应激环境可能通过肥大细胞衍生的KGF表达扰乱皮肤屏障稳态。