Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes
Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes
复制标题
沙利度胺可改善红斑痤疮样皮肤炎症并抑制角质形成细胞中 NF-kappaB 的激活。
DOI：
10.1016/j.biopha.2019.109011
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发表时间：
2019-08-01
影响因子：
7.5
通讯作者：
Deng, Zhili
中科院分区：
文献类型：
--
作者：
Chen, Mengting;Xie, Hongfu;Deng, Zhili
背景：酒渣鼻是一种病因不明的慢性炎症性皮肤病。有证据表明，其潜在的发病机制是由异常炎症和血管反应调节的。沙利度胺是一种人工合成的衍生酸，具有抗炎和抗血管生成的特性。目的：探讨沙利度胺对酒渣鼻病变的影响及其分子机制。方法：皮内注射LL37诱导小鼠酒渣鼻样变，同时腹腔注射沙利度胺。评估皮肤炎的严重程度。采用定量聚合酶链式反应检测酒渣鼻相关细胞因子和趋化因子的基因表达水平。免疫荧光、定量聚合酶链式反应和酶联免疫吸附试验检测CD4阳性T辅助细胞和CD31阳性微血管的数量及相关基因的表达。结果：沙利度胺可明显减轻LL37诱导的酒渣鼻模型小鼠真皮红斑形成，减少炎症细胞的浸润。沙利度胺可抑制LL37诱导的小鼠皮肤和HaCaT角质形成细胞产生的细胞因子和趋化因子。特别是，我们发现沙利度胺减少了CD4(+)T辅助细胞的渗透，并下调了Th1和Th17极化基因。此外，沙利度胺治疗还降低了微血管密度和血管内皮生长因子(VEGF)的表达。我们进一步证实了沙利度胺在LL37处理的皮肤和在肿瘤坏死因子α刺激的HaCaT角质形成细胞中抑制了核因子-kappaB的激活。结论：沙利度胺可以减轻皮肤的炎症并抑制核因子-kappaB的激活，从而推测沙利度胺可能是一种治疗酒渣鼻的新药物。
Background: Rosacea is a chronic inflammatory skin disorder of uncertain etiology. Evidence suggests the underlying pathogenesis is modulated by abnormal inflammatory and vascular responses. Thalidomide is a synthetic derivative acid with anti-inflammatory and anti-angiogenic properties. However, its effects on rosacea remain unknown.Objectives: To investigate the effects of thalidomide on the lesional alterations and molecular mechanisms in rosacea.Methods: Mice were intradermally injected with LL37 to induce rosacea-like features and intraperitoneally administered with thalidomide. The severity of skin inflammation was evaluated. The mRNA levels of cytokines and chemokines associated with rosacea were assessed by qPCR. The number of CD4 positive infiltrated T helper cells and CD31 positive microvessels, and related-genes were measured by immunofluorescence, qPCR and ELISA. Moreover, the effect of thalidomide on inhibiting NF-kappa B activation was determined by immunofluorescence and western blot.Results: Our results showed that thalidomide significantly alleviated erythema and reduced inflammatory cell infiltration in dermis of LL37-induced rosacea-like mice. The production of cytokines and chemokines induced by LL37 was decreased by thalidomide in mice skin and HaCaT keratinocytes. Particularly, we showed thalidomide reduced CD4(+) T helper cell infiltration and downregulated Th1- and Th17-polarizing genes. In addition, thalidomide treatment lowered the microvessel density and vascular endothelial growth factor (VEGF) expression. We further demonstrated that thalidomide suppressed NF-kappa B activation in LL37-treated skin and in TNF-alpha-astimulated HaCaT keratinocytes in vitro.Conclusions: Our findings suggest thalidomide attenuates the inflammation and represses NF-kappa B activation in skin, which leads to assumptions that thalidomide may be a new therapeutic agent for rosacea.