Wang Dan, Han Lina
Neonatology Department, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Exp Ther Med. 2021 Apr;21(4):350. doi: 10.3892/etm.2021.9781. Epub 2021 Feb 11.
Neonatal sepsis (NS) remains a global problem. In the present study, abnormal expression of microRNA-1184 (miR-1184) was detected in neonates with NS and it was endeavored to investigate the diagnostic value of miR-1184, as well as its regulatory role in lipopolysaccharide (LPS)-induced inflammatory response . Furthermore, the correlation between interleukin-16 (IL-16) and miR-1184 was investigated to elucidate the pathological mechanisms of NS development. Reverse transcription-quantitative PCR was used to detect the expression of miR-1184. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of miR-1184 in NS. Furthermore, a sepsis cell model was established by using LPS-induced monocytes to explore the effect of miR-1184 on the inflammatory response. The levels of inflammatory cytokines were determined by ELISA. A luciferase reporter assay was used to investigate the direct targeting interaction between miR-1184 and IL-16. The results indicated that the serum levels of miR-1184 in neonates with sepsis were decreased and miR-1184 had a high diagnostic value when differentiating NS from respiratory conditions in neonates. , the expression of miR-1184 in monocytes was inhibited by LPS and overexpression of miR-1184 reversed the effect of LPS to stimulate the inflammatory response. IL-16 was demonstrated to be a target of miR-1184 and a negative correlation between them was identified in patients with NS. The inflammatory response inhibited by miR-1184 mimics was enhanced by overexpression of IL-16 in LPS-induced monocytes. In conclusion, decreased levels of serum miR-1184 may be a potential diagnostic biomarker for NS. In addition, miR-1184 inhibited the LPS-induced inflammatory response by targeting IL-16 in monocytes, suggesting that the miR-1184/IL-16 axis may be a potential therapeutic target for NS.
新生儿败血症(NS)仍然是一个全球性问题。在本研究中,检测到NS新生儿中微小RNA-1184(miR-1184)表达异常,并致力于研究miR-1184的诊断价值及其在脂多糖(LPS)诱导的炎症反应中的调节作用。此外,研究了白细胞介素-16(IL-16)与miR-1184之间的相关性,以阐明NS发生发展的病理机制。采用逆转录定量PCR检测miR-1184的表达。进行受试者工作特征曲线分析以评估miR-1184在NS中的诊断价值。此外,通过使用LPS诱导的单核细胞建立败血症细胞模型,以探讨miR-1184对炎症反应的影响。通过酶联免疫吸附测定法测定炎性细胞因子水平。使用荧光素酶报告基因测定法研究miR-1184与IL-16之间的直接靶向相互作用。结果表明,败血症新生儿血清miR-1184水平降低,且在区分新生儿NS与呼吸道疾病时,miR-1184具有较高的诊断价值。LPS抑制单核细胞中miR-1184的表达,miR-1184过表达可逆转LPS刺激炎症反应的作用。IL-16被证明是miR-1184的靶点,且在NS患者中发现两者呈负相关。在LPS诱导的单核细胞中,IL-16过表达增强了miR-1184模拟物抑制的炎症反应。总之,血清miR-1184水平降低可能是NS的潜在诊断生物标志物。此外,miR-1184通过靶向单核细胞中的IL-16抑制LPS诱导的炎症反应,提示miR-1184/IL-16轴可能是NS的潜在治疗靶点。