IL-18 knockout alleviates atopic dermatitis-like skin lesions induced by MC903 in a mouse model
IL-18 knockout alleviates atopic dermatitis-like skin lesions induced by MC903 in a mouse model
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DOI：
10.3892/ijmm.2020.4630
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发表时间：
2020-08-01
影响因子：
5.4
通讯作者：
Qi, Rui-Qun
中科院分区：
文献类型：
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作者：
Chen, Jia-Long;Niu, Xue-Li;Qi, Rui-Qun
白细胞介素(IL)-18是一种促炎细胞因子，在许多皮肤疾病中起重要作用。本研究的目的是探讨IL-18在特应性皮炎（AD）发展中的作用。为此，将小鼠分为4组（n=5/组）：i)野生型（WT）对照；ii) il - 18敲除（KO）对照；iii) mc903处理的WT小鼠；iv) mc903处理的KO小鼠。将MC903 （4 nmol乙醇）连续15天，每天局部涂抹于暴露在外的小鼠皮肤上。通过AD评分（SCORAD）评估AD样症状和严重程度。采用酶联免疫吸附法测定血清免疫球蛋白E （IgE）和胸腺基质淋巴生成素（TSLP）水平。采用免疫组化方法检测皮肤病变组织中IL-1 β、转录激活因子STAT 3和聚丝蛋白FLG的表达。RT-qPCR检测皮肤病变组织中IL-1 β、IL-4、IL-9、STAT3、促肾上腺皮质激素释放激素受体（CRHR）1、CRHR2、TSLP和caspase-1 mRNA水平。结果表明，IL-18在ad样病变的发展中可能是一种多效促炎细胞因子。IL-18 KO减轻MC903诱导的ad样病变加重，部分原因是通过上调Th2细胞因子。IL-18促进ad样病变表皮FLG和CRHR2的表达，下调血清IgE水平。总体而言，本研究结果表明IL-18缺乏可减轻小鼠ad诱导的病变。
Interleukin (IL)-18, a pro-inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL-18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild-type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903-treated WT mice; and iv) MC903-treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD-like symptoms and severity were evaluated by the scoring of AD (SCORAD). Serum immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP) levels were determined with the use of an enzyme-linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL-1 beta, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT-qPCR was performed to assess the mRNA levels of IL-1 beta, IL-4, IL-9, STAT3, corticotropin-releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase-1 in the skin lesions. It was demonstrated that IL-18 may function as a pleiotropic pro-inflammatory cytokine in the development of AD-like lesions. IL-18 KO reduced aggravated AD-like lesions induced by MC903, in part by upregulating Th2 cytokines. IL-18 promoted the expression of FLG in the epidermis and CRHR2 in AD-like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL-18 deficiency alleviates AD-induced lesions in mice.