重症肺炎儿童血清IL-17B升高及其介导人支气管上皮细胞表达IL-6的免疫机制研究

Elevated Serum IL-17B in Children with Severe Pneumonia and Mediates IL-6 Expression in Human Bronchial Epithelial Cells

IL-17B是IL-17家族中的一员,参与了多种炎性疾病,但其在肺部炎症疾病中的研究较少。该研究检测了重症肺炎儿童血清中IL-17B的浓度,发现其较健康对照组显著升高。为进一步研究IL-17B与肺部炎症的关系,将IL-17B作用于人支气管上皮细胞。结果发现,经IL-17B刺激后,HBEC表达IL-6的水平明显升高,且具有时间和剂量依赖性;随后,通过信号通路抑制剂筛选以及Western blot检测细胞内信号通路蛋白磷酸化水平进行验证,发现IL-17B是通过活化P38 MAPK、ERK、JAK、NF-κB信号通路,进而上调人支气管上皮细胞表达IL-6。最后,再次检测了重症肺炎儿童血清中IL-6的水平,其浓度显著高于健康对照组;此外,还对其进行了相关性分析,发现重症肺炎儿童的IL-17B和IL-6水平呈显著正相关。以上结果表明,肺部炎症感染时,IL-17B能通过激活相关信号通路上调IL-6水平,进而促进免疫应答。研究IL-17B在肺部炎症感染中发挥的免疫效应有助于了解肺部感染免疫的进程,进而为临床提供有效的治疗策略。

IL-17B belongs to IL-17 family and is involved in a variety of inflammatory diseases,but the role of IL-17B in regulating pulmonary inflammation in lung diseases is still unknown.Serum IL-17B concentration in children with severe pneumonia was significantly higher than healthy control group.To further investigate the relationship between IL-17B and pulmonary inflammation,IL-17B was applied to human bronchial epithelial cells.The results showed that remarkably elevated IL-6 was measured in the supernatant of bronchial epithelial cells stimulated with IL-17B in a time-and dose-dependent manner.Subsequently,inhibitors of signaling pathways were used for screening related pathways and these results were further validated by Western blot.Our results indicated that IL-17B could upregulate IL-6 production by activating p38 MAPK,ERK,JAK and NF-κB pathways in human bronchial epithelial cells.Moreover,serum level of IL-6 was significantly higher in children with severe pneumonia than healthy control group.In addition,we found increased level of IL-17B positively correlated with IL-6 in children with severe pneumonia.In conclusion,IL-17B could upregulate of IL-6 thereby promoting immune responses in children pneumonia,which might shed light for the development of cytokine-based treatment of children pneumonia.