PDF(Pubmed)
Abstract：
Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an in vitro cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1β, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1β, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1β, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.
摘要：
特应性皮炎(AD)是一种常见的炎性皮肤病,并且是与世界范围内的皮肤病相关的发病的主要原因。对于大多数患者来说，AD是一种不能完全治愈的终生疾病。因此,在本研究中，使用生物信息学技术筛选表皮免疫微环境中的差异表达基因（DEGs）。随后，构建体外细胞模型以研究microRNA(miR)-155在AD免疫浸润中的作用.在本研究中,从基因表达Omnibus下载了两个数据集（GSE121212和GSE157194），在筛选DEGs并进行基因本体论和京都百科全书的基因和基因组功能富集分析之前。在发现的差异表达基因中，使用miRNet预测miR-155可能的靶基因。因此,肽酶抑制剂3（PI3），FOS样1，AP-1转录因子亚基（FOSL1），选择C-X-C基序趋化因子配体(CXCL)1和CXCL8作为miR-155在AD患者表皮免疫微环境中的潜在靶基因。同时,通过TNF-α和IFN-γ处理构建使用HaCaT细胞的炎症细胞模型。miR-155对HaCaT细胞增殖及分泌IL-1β的影响,然后分析炎症和非炎症条件下的IL-6、IL-10、IL-15、PI3、FOSL1、CXCL1和CXCL8。结果表明，miR-155转染HaCaT细胞后，miR-155抑制HaCaT细胞增殖，降低PI3和CXCL8的mRNA表达水平，增加FOSL1的mRNA水平和IL-1β的分泌水平，IL-6、IL-15和CXCL1。相比之下,miR-155降低IL-10和CXCL8的分泌水平。在HaCaT细胞的炎症细胞模型中，发现miR-155在炎症过程中显著抑制HaCaT细胞的增殖，同时显著增加IL-1β的分泌，IL-6、IL-10和IL-15。此外,miR-155增加了CXCL1和CXCL8的mRNA表达和分泌水平，同时也增加了PI3的mRNA表达水平。目前的研究结果表明，miR-155可以刺激角质形成细胞产生炎症细胞因子和蛋白质，从而增强AD的炎症反应。
