摘要
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.
作者
周洁
曾秋丽
陈大鹏
ZHOU Jie;ZENG Qiuli;CHEN Dapeng(Department of Clinical Laboratory,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders(Chongqing),China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Children’s Hospital of Chongqing Medical University,Chongqing 400016,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2019年第12期2282-2290,共9页
Chinese Journal of Cell Biology
基金
重庆市自然科学基金(批准号:cstc2018jcyjAX0780)资助的课题.
