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
AIM To study the genetic association and epistatic interaction of the interleukin(IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A total of 159 pediatric inflammatory IBD patient...AIM To study the genetic association and epistatic interaction of the interleukin(IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A 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 IL10 RA,IL10 RB,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 highorder epistasis between combinations of the individual SNPs. RESULTS The 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 IL10 RA,IL10 RB,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-10 RB rs2834167 and HO1 rs2071746(dominant-additive,P = 0.0018,Bp = 0.039); and(3) among IL-10 rs1800872,IL10 RB rs2834167,and HO1 rs2071746(additivedominant-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 IL10 RA,IL10 RB,and HO1 genes(additive-dominant-additive,P = 0.008,Bp = 0.287).CONCLUSION These 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
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AIM To study the genetic association and epistatic interaction of the interleukin(IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A 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 IL10 RA,IL10 RB,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 highorder epistasis between combinations of the individual SNPs. RESULTS The 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 IL10 RA,IL10 RB,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-10 RB rs2834167 and HO1 rs2071746(dominant-additive,P = 0.0018,Bp = 0.039); and(3) among IL-10 rs1800872,IL10 RB rs2834167,and HO1 rs2071746(additivedominant-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 IL10 RA,IL10 RB,and HO1 genes(additive-dominant-additive,P = 0.008,Bp = 0.287).CONCLUSION These 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.
