In vitro human monocyteline U937 cells were inoculated with HSV1, which were persistently treated with 10 μg/ml LPS or/and 10 3 U/ml rhGMCSF as well as 10 3 U/ml rhIL3 since two days before inoculation. The effects o...In vitro human monocyteline U937 cells were inoculated with HSV1, which were persistently treated with 10 μg/ml LPS or/and 10 3 U/ml rhGMCSF as well as 10 3 U/ml rhIL3 since two days before inoculation. The effects of GMCSF and IL3 on the resistance of U937 cells to HSV1 were studied by microcytopathy assay for the infective titers of the cell culture supernatans(TCID 50 ). The results showed that at the 4 th day after inoculation the mean titers of GMCSF group and IL3 group were lower 44 and 21 fold than that of control group, respectively. The inhibition of HSV1 replication in LPSstimulated U937 cells induced by GMCSF or by IL3 was more significant. 2, 4, 6 and 8 days after inoculation, the mean titers of GMCSF+LPS group were lower 74, 162, 15 and 11 fold, and those of IL3+LPS group were lower 89, 18, 59 and 10 fold than that of only LPS treated group, respectively. These data indicate that GMCSF and IL3 could antagonise the enhancement activity of LPS for the virus replication in the cells and increase the resistance of U937 cells to HSV1.展开更多
To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (...To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.展开更多
信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)是细胞增殖转移的重要调节因子,参与多种恶性肿瘤的发生和发展,是目前靶向抗肿瘤药物研究的热点之一。本课题组通过两面神激酶(Janus kinase,JAK)/S...信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)是细胞增殖转移的重要调节因子,参与多种恶性肿瘤的发生和发展,是目前靶向抗肿瘤药物研究的热点之一。本课题组通过两面神激酶(Janus kinase,JAK)/STAT3通路抑制剂筛选模型筛选得到了新型苯并二咪唑结构小分子化合物LZJ541,具有明确的STAT3抑制活性。通过MTT实验检测LZJ541对肝癌HepG2及前列腺癌PC-3细胞增殖能力的影响;通过Western blot实验检测其对肿瘤细胞中STAT3通路相关蛋白的影响;通过流式细胞术检测其对HepG2细胞凋亡水平及周期分布的影响。结果表明,LZJ541显著抑制STAT3信号通路的活化,能显著抑制HepG2细胞增殖,其半数抑制浓度(half maximal inhibitory concentration,IC_(50))为13.8μmol·L^(-1)远低于STAT3低表达的PC-3细胞(IC_(50):41.99μmol·L-1),LZJ541还可抑制HepG2细胞中STAT3蛋白的磷酸化,从而诱导细胞凋亡和周期阻滞,发挥抗肿瘤作用。综上,LZJ541具有一定的体外抗肿瘤作用,本研究为围绕这一化合物研发新型STAT3靶向抗肿瘤药物提供了实验依据。展开更多
文摘In vitro human monocyteline U937 cells were inoculated with HSV1, which were persistently treated with 10 μg/ml LPS or/and 10 3 U/ml rhGMCSF as well as 10 3 U/ml rhIL3 since two days before inoculation. The effects of GMCSF and IL3 on the resistance of U937 cells to HSV1 were studied by microcytopathy assay for the infective titers of the cell culture supernatans(TCID 50 ). The results showed that at the 4 th day after inoculation the mean titers of GMCSF group and IL3 group were lower 44 and 21 fold than that of control group, respectively. The inhibition of HSV1 replication in LPSstimulated U937 cells induced by GMCSF or by IL3 was more significant. 2, 4, 6 and 8 days after inoculation, the mean titers of GMCSF+LPS group were lower 74, 162, 15 and 11 fold, and those of IL3+LPS group were lower 89, 18, 59 and 10 fold than that of only LPS treated group, respectively. These data indicate that GMCSF and IL3 could antagonise the enhancement activity of LPS for the virus replication in the cells and increase the resistance of U937 cells to HSV1.
基金Supported by a Children Miracle Network Research Grant,No.132698 to Lin Z(P.I.)and Thomas NJ(Co-P.I.)(2011-2013)and Floros J(P.I.)(2013-2014)
文摘To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.
