The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗...目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗后Hp C 13呼气实验。采用Pearson相关性分析,Hp胃溃疡患者Hp根除率与患者治疗前血清IL-8、IL-17水平间的相关性。结果治疗3个疗程后,Hp阳性胃溃疡患者血清IL-8、IL-17水平水平较治疗前明显下降,Hp根除率为70.11%,治疗前观察组血清IL-8、IL-17水平明显低于对照组(P<0.05);不同年龄、不同胃溃疡病程、既往抗Hp治疗史的Hp阳性胃溃疡患者血清IL-8、IL-17水平及Hp根除率比较均有差异(P<0.05);Hp阳性胃溃疡患者治疗前血清IL-8、IL-17水平与Hp根除率呈负相关(r=-0.613、-0.497,P<0.01)。结论Hp阳性胃溃疡患者治疗后Hp根除率与治疗前血清IL-8、IL-17水平呈负相关,提示临床对Hp阳性胃溃疡患者治疗时应关注机体细胞因子IL-8、IL-17水平,并辅以改善相应的治疗措施,以提升Hp根除率。展开更多
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
文摘目的探讨血清IL-8、IL-17对Hp阳性胃溃疡患者Hp根除率的影响。方法共174例在我院就诊的的Hp阳性胃溃疡患者,均行胃溃疡常规治疗及抗Hp三联疗法治疗。治疗前、完成3个治疗疗程后,采集患者血液检测血清IL-8、IL-17水平,并对所有患者行治疗后Hp C 13呼气实验。采用Pearson相关性分析,Hp胃溃疡患者Hp根除率与患者治疗前血清IL-8、IL-17水平间的相关性。结果治疗3个疗程后,Hp阳性胃溃疡患者血清IL-8、IL-17水平水平较治疗前明显下降,Hp根除率为70.11%,治疗前观察组血清IL-8、IL-17水平明显低于对照组(P<0.05);不同年龄、不同胃溃疡病程、既往抗Hp治疗史的Hp阳性胃溃疡患者血清IL-8、IL-17水平及Hp根除率比较均有差异(P<0.05);Hp阳性胃溃疡患者治疗前血清IL-8、IL-17水平与Hp根除率呈负相关(r=-0.613、-0.497,P<0.01)。结论Hp阳性胃溃疡患者治疗后Hp根除率与治疗前血清IL-8、IL-17水平呈负相关,提示临床对Hp阳性胃溃疡患者治疗时应关注机体细胞因子IL-8、IL-17水平,并辅以改善相应的治疗措施,以提升Hp根除率。