Laboratory of Mucosal Immunology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Mol Med Rep. 2019 Mar;19(3):2413-2420. doi: 10.3892/mmr.2019.9864. Epub 2019 Jan 15.
Calprotectin in mucosal epidermal keratinocytes has an important role in fighting microbial infections. S100A8 belongs to the S100 protein family and is a subunit of calprotectin (heterodimer complex of S100A8/A9). Interleukin‑1α (IL‑1α) is one of the cytokines produced by oral keratinocytes. The primary aims of the present study were to investigate the effect of IL‑1α on the expression of S100A8 and its underlying molecular mechanism in oral epithelial cells. Determining the molecular mechanism of the induced expression of S100A8 by IL‑1α aims to improve current understanding of the roles of calprotectin during the infection of mucosal epithelial cells. The expression analysis indicated that IL‑1α significantly induced the expression of S100A8 in human TR146 epithelial cells at the mRNA and protein levels, respectively. The reporter assay demonstrated that the upregulatory effect of S100A8 induced by IL‑1α was dependent on the S100A8 promoter specific region (‑165/‑111). The results of electrophoresis mobility shift assay and chromatin immunoprecipitation assay also demonstrated that the CCAAT/enhancer binding protein β (C/EBPβ) binding site (‑113/‑109) in the S100A8 promoter region was involved into the upregulatory effect on the expression of S100A8 induced by IL‑1α. Taken together, these results suggested that the activation of the expression of S100A8 induced by IL‑1α in TR146 epithelial cells involves a mechanism by which the binding activity of C/EBPβ to the specific site (‑113/‑109) of the S100A8 promoter is increased.
钙卫蛋白在黏膜表皮角质形成细胞中对于抵抗微生物感染具有重要作用。S100A8 属于 S100 蛋白家族,是钙卫蛋白(S100A8/A9 异二聚体复合物)的一个亚基。白细胞介素-1α(IL-1α)是口腔角质形成细胞产生的细胞因子之一。本研究的主要目的是探讨 IL-1α 对口腔上皮细胞中 S100A8 表达的影响及其潜在的分子机制。确定 IL-1α 诱导 S100A8 表达的分子机制旨在提高对钙卫蛋白在黏膜上皮细胞感染过程中作用的认识。表达分析表明,IL-1α 分别在 mRNA 和蛋白水平上显著诱导人 TR146 上皮细胞中 S100A8 的表达。报告基因检测表明,IL-1α 诱导的 S100A8 上调作用依赖于 S100A8 启动子特异区(-165/-111)。电泳迁移率变动分析和染色质免疫沉淀分析的结果也表明,S100A8 启动子区域的 CCAAT/增强子结合蛋白β(C/EBPβ)结合位点(-113/-109)参与了 IL-1α 诱导的 S100A8 表达上调。综上所述,这些结果表明,IL-1α 激活 TR146 上皮细胞中 S100A8 表达涉及 C/EBPβ 与 S100A8 启动子特定位点(-113/-109)结合活性增加的机制。