AIM To investigate interferon-γ-inducible protein-10's(IP-10) potential to anticipate rapid(RVR)-and sustained virological responses(SVR) to chronic hepatitis C(CHC) treatment.METHODS We included case series exam...AIM To investigate interferon-γ-inducible protein-10's(IP-10) potential to anticipate rapid(RVR)-and sustained virological responses(SVR) to chronic hepatitis C(CHC) treatment.METHODS We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC,in patients treatment free for at least six months,with genotype 1 or 4,and in relation to 24 wk treatment for genotype 2 and 3,with pegylated interferon in combination with ribavirin.Patients had to have both a baseline IP-10 level as well as a hepatitis C virus(HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment.Studies including patients with liver diseases other than CHC,human immunodeficiency virus-infection,treatment with immunosuppresents or cytostatica,alcohol dependency or active intravenous drug-use were excluded.We found 81 articles by searching the MEDLINE and EMBASE databases.Eight studies were eligible for inclusion.Their quality were assesed using an 18 point checklist for case series,developed using a modified Delphi technique.Information was extracted from the articles,and no raw data was requisitioned.The review protocol wasregistered at the International Prospective Register of Systematic Reviews(reg.number:CRD42014008736).RESULTS Three studies reported on baseline IP-10 level in association with RVR.A signigficant association was found for HCV genotype 1 infection by two studies.Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients,respectively.A trend was seen for an association between RVR and baseline IP-10 for genotype 4,while no association was found for genotype 2 and 3.Seven studies provided information regarding baseline IP-10 and SVR.Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV,genotype 1 infected patients showed a significant association.Likewise a significant association was seen for HCV,genotype 4 infected,while no association was found for HCV,genotype 2 and 3 infected.Though only two studies examined the assosiation for HCV genotype 4 infected and HCV genotype 2 and 3 infected respectively.CONCLUSION We found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4.展开更多
目的:研究SARS冠状病毒S蛋白诱导呼吸道上皮细胞合成释放IP-10(interferon-gamma induc-ible protein 10)的信号分子机制。方法:通过基因芯片检测SARS冠状病毒的S蛋白作用于人支气管上皮细胞16HBE后信号通路基因表达谱的变化;采纳RT-PCR...目的:研究SARS冠状病毒S蛋白诱导呼吸道上皮细胞合成释放IP-10(interferon-gamma induc-ible protein 10)的信号分子机制。方法:通过基因芯片检测SARS冠状病毒的S蛋白作用于人支气管上皮细胞16HBE后信号通路基因表达谱的变化;采纳RT-PCR、EMSA、Western blotting等方法进一步分析JAK-STAT通路中信号分子的磷酸化、IRF-1和IP-10基因表达的变化及其相应信号分子抑制剂对表达水平的影响。结果:S蛋白作用于人支气管上皮细胞16HBE诱导了JAK-STAT信号通路涉及的重要转录因子基因IRF-1的表达,该信号通路的转录因子STAT1在刺激后15 min发生磷酸化,2 h即可检出IP-10基因的表达,IP-10的表达可以完全被STAT1、JAK2抑制剂阻断。EMSA显示:支气管上皮细胞在S蛋白的作用下,其核蛋白能够特异性与ISRE和GASDNA基序相结合,而不能与NF-κB的DNA基序相结合。结论:SARS-CoV的S蛋白通过激活JAK-STAT信号转导通路诱导IP-10在宿主细胞的生成。提示病毒诱导的JAK-STAT信号通路激活在病毒感染相关的急性肺损伤发生中具有重要地位。展开更多
基金Supported by Amagar and Hvidovre Hospital Research Foun-dation of 45000 Dkr.(to Bastian Neesgaard)The Family Hede Nielsen Foundation of 10000 Dkr.(to Bastian Neesgaard)
文摘AIM To investigate interferon-γ-inducible protein-10's(IP-10) potential to anticipate rapid(RVR)-and sustained virological responses(SVR) to chronic hepatitis C(CHC) treatment.METHODS We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC,in patients treatment free for at least six months,with genotype 1 or 4,and in relation to 24 wk treatment for genotype 2 and 3,with pegylated interferon in combination with ribavirin.Patients had to have both a baseline IP-10 level as well as a hepatitis C virus(HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment.Studies including patients with liver diseases other than CHC,human immunodeficiency virus-infection,treatment with immunosuppresents or cytostatica,alcohol dependency or active intravenous drug-use were excluded.We found 81 articles by searching the MEDLINE and EMBASE databases.Eight studies were eligible for inclusion.Their quality were assesed using an 18 point checklist for case series,developed using a modified Delphi technique.Information was extracted from the articles,and no raw data was requisitioned.The review protocol wasregistered at the International Prospective Register of Systematic Reviews(reg.number:CRD42014008736).RESULTS Three studies reported on baseline IP-10 level in association with RVR.A signigficant association was found for HCV genotype 1 infection by two studies.Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients,respectively.A trend was seen for an association between RVR and baseline IP-10 for genotype 4,while no association was found for genotype 2 and 3.Seven studies provided information regarding baseline IP-10 and SVR.Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV,genotype 1 infected patients showed a significant association.Likewise a significant association was seen for HCV,genotype 4 infected,while no association was found for HCV,genotype 2 and 3 infected.Though only two studies examined the assosiation for HCV genotype 4 infected and HCV genotype 2 and 3 infected respectively.CONCLUSION We found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4.
