Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Int J Mol Med. 2019 Oct;44(4):1436-1446. doi: 10.3892/ijmm.2019.4295. Epub 2019 Jul 31.
Toll‑like receptors (TLRs), which are a class of pattern‑recognition receptors, can sense specific molecules of pathogens and then activate immune cells, such as neutrophils. The regulation of TLR signaling in immune cells has been investigated by various studies. However, the interaction of TLR signaling‑activated microRNAs (miRNAs) and genes has not been well investigated in a specific type of immune cells. In the present study, neutrophils were isolated from peripheral blood of a healthy donor, and then treated for 16 h with Staphylococcus aureus lipoteichoic acid (LTA), which is an agonist of TLR2. The miRNA and mRNA expression profiles were analyzed via next‑generation sequencing and bioinformatics approaches. A total of 290 differentially expressed genes between LTA‑treated and vehicle‑treated neutrophils were identified. Gene ontology analysis revealed that various biological processes and pathways, including inflammatory responses, defense response, positive regulation of cell migration, motility, and locomotion, and cell surface receptor signaling pathway, were significantly enriched. In addition, 38 differentially expressed miRNAs were identified and predicted to be involved in regulating signal transduction and cell communication. The interaction of 4 miRNAs (hsa‑miR‑34a‑5p, hsa‑miR‑34c‑5p, hsa‑miR‑708‑5p, and hsa‑miR‑1271‑5p) and 5 genes (MET, CACNB3, TNS3, TTYH3, and HBEGF) was proposed to participate in the LTA‑induced signaling network. The present findings may provide novel information for understanding the detailed expression profiles and potential networks between miRNAs and their target genes in LTA‑stimulated healthy neutrophils.
toll 样受体（TLRs）是一类模式识别受体，能够识别病原体的特定分子，然后激活免疫细胞，如中性粒细胞。已经有许多研究探讨了 TLR 信号在免疫细胞中的调控。然而，在特定类型的免疫细胞中，TLR 信号激活的 microRNAs（miRNAs）和基因之间的相互作用尚未得到充分研究。本研究中，从健康供者的外周血中分离中性粒细胞，然后用金黄色葡萄球菌脂磷壁酸（LTA）处理 16 小时，LTA 是 TLR2 的激动剂。通过下一代测序和生物信息学方法分析 miRNA 和 mRNA 表达谱。共鉴定出 LTA 处理和载体处理的中性粒细胞之间 290 个差异表达基因。基因本体分析显示，各种生物学过程和途径，包括炎症反应、防御反应、细胞迁移、运动和运动的正调节，以及细胞表面受体信号通路，显著富集。此外，还鉴定出 38 个差异表达的 miRNA，并预测它们参与调节信号转导和细胞通讯。提出了 4 个 miRNA（hsa-miR-34a-5p、hsa-miR-34c-5p、hsa-miR-708-5p 和 hsa-miR-1271-5p）和 5 个基因（MET、CACNB3、TNS3、TTYH3 和 HBEGF）之间的相互作用，参与 LTA 诱导的信号网络。本研究结果可能为理解 LTA 刺激健康中性粒细胞中 miRNA 及其靶基因之间的详细表达谱和潜在网络提供新的信息。
