目的探讨IL-17RA在人肝细胞癌(hepatocellular carcinoma,HCC)组织中表达情况及其对肝肿瘤切除患者预后的影响,并评价其对HCC细胞株生物学特性的影响。方法收集163例HCC组织并制成组织芯片,免疫组化染色法检测肿瘤组织中IL-17RA的表达情...目的探讨IL-17RA在人肝细胞癌(hepatocellular carcinoma,HCC)组织中表达情况及其对肝肿瘤切除患者预后的影响,并评价其对HCC细胞株生物学特性的影响。方法收集163例HCC组织并制成组织芯片,免疫组化染色法检测肿瘤组织中IL-17RA的表达情况,Kaplan-Meier法和Cox回归模型分析患者总生存期的影响因素。采用siRNA瞬时转染高侵袭性肝癌细胞株MHCC-97H和Huh7以下调IL-17RA的表达,用划痕实验、Transwell侵袭实验检测转染前后MHCC-97H和Huh7细胞株迁移、侵袭能力,用CCK8方法检测转染前后奥沙利铂对MHCC-97H和Huh7细胞株的抑制率。结果肿瘤直径大于10 cm (HR=1.820, P =0.028)、合并癌栓(HR=2.087, P=0.003)以及IL-17RA高表达(HR=1.579, P =0.042)是影响HCC患者术后总生存期的独立危险因素;siRNA瞬时转染下调HCC细胞株MHCC-97H和Huh7的IL-17RA表达后,肿瘤细胞的迁移、侵袭能力明显下降,奥沙利铂对肿瘤细胞的抑制率显著提高。结论 IL-17RA高表达是影响HCC患者术后生存的独立危险因素,抑制其表达可以降低HCC细胞株的迁移、侵袭能力,提高奥沙利铂对肝癌细胞株的抑制率。展开更多
目的研究白细胞介素17受体A(Interleukin-17receptor type A,IL-17RA)在非小细胞肺癌中的表达及其与预后的关系。方法收集2010年1月1日-2013年12月31日在新疆医科大学附属肿瘤医院胸外科接受标准肺癌根治术且随访资料完整的131例肺鳞癌...目的研究白细胞介素17受体A(Interleukin-17receptor type A,IL-17RA)在非小细胞肺癌中的表达及其与预后的关系。方法收集2010年1月1日-2013年12月31日在新疆医科大学附属肿瘤医院胸外科接受标准肺癌根治术且随访资料完整的131例肺鳞癌和腺癌患者的术后标本,采用免疫组织化学法检测癌组织、癌旁组织中IL-17RA的表达情况。Kaplan-Meier法比较癌组织IL-17RA高表达和低表达对患者3年无病生存期(Disease-free survival,DFS)的影响。结果 IL-17RA在癌组织的表达高于癌旁组织(P<0.001);IL-17RA的表达与病理类型、肿瘤直径和术后病理分期(pTNM stages,pTNM)有关(P<0.05);生存分析显示,癌组织IL-17RA低表达患者的DFS均优于IL-17RA高表达者(P=0.032);COX回归分析结果显示,IL-17RA阳性表达是肺鳞癌、腺癌患者DFS的重要影响因素(P=0.041,HR=1.683)。结论 IL-17RA表达是非小细胞肺癌患者独立预后因素,高表达提示预后差。展开更多
Interleukin 17(IL-17)is an important cytokine that can induce tissue inflammation and is involved in the pathogenesis of numerous autoimmune diseases.However,the regulation of its signaling transduction has not been w...Interleukin 17(IL-17)is an important cytokine that can induce tissue inflammation and is involved in the pathogenesis of numerous autoimmune diseases.However,the regulation of its signaling transduction has not been well described.In this study,we report that thousand and one kinase 1(TAOK1)functions as a negative regulator of IL-17-mediated signal transduction and inflammation.TAOK1 knockdown promotes IL-17-induced cytokine and chemokine expression and the activation of mitogen-activated protein kinases and nuclear factor-κB.We further demonstrate that TAOK1 interacts with IL-17 receptor A(IL-17RA)independent of its kinase activity,and TAOK1 dose-dependently prevents the formation of the IL-17R-Act1(nuclear factor activator 1,also known as tumor necrosis factor receptor-associated factor 3 interacting protein 2)complex.Consistent with this,TAOK1 deficiency exacerbates colitis in the 2,4,6-trinitrobenzenesulfonic acid-induced experimental model of inflammatory bowel disease,likely by its promotion of the IL-17-mediated signaling pathway.TAOK1 expression is decreased in the colons of ulcerative colitis patients.In conclusion,these findings suggest that TAOK1 is involved in the development of IL-17-related autoimmune disorders.展开更多
Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the...Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.展开更多
文摘目的探讨IL-17RA在人肝细胞癌(hepatocellular carcinoma,HCC)组织中表达情况及其对肝肿瘤切除患者预后的影响,并评价其对HCC细胞株生物学特性的影响。方法收集163例HCC组织并制成组织芯片,免疫组化染色法检测肿瘤组织中IL-17RA的表达情况,Kaplan-Meier法和Cox回归模型分析患者总生存期的影响因素。采用siRNA瞬时转染高侵袭性肝癌细胞株MHCC-97H和Huh7以下调IL-17RA的表达,用划痕实验、Transwell侵袭实验检测转染前后MHCC-97H和Huh7细胞株迁移、侵袭能力,用CCK8方法检测转染前后奥沙利铂对MHCC-97H和Huh7细胞株的抑制率。结果肿瘤直径大于10 cm (HR=1.820, P =0.028)、合并癌栓(HR=2.087, P=0.003)以及IL-17RA高表达(HR=1.579, P =0.042)是影响HCC患者术后总生存期的独立危险因素;siRNA瞬时转染下调HCC细胞株MHCC-97H和Huh7的IL-17RA表达后,肿瘤细胞的迁移、侵袭能力明显下降,奥沙利铂对肿瘤细胞的抑制率显著提高。结论 IL-17RA高表达是影响HCC患者术后生存的独立危险因素,抑制其表达可以降低HCC细胞株的迁移、侵袭能力,提高奥沙利铂对肝癌细胞株的抑制率。
基金supported by grants from the National Key Research and Development Program of China(2016YFA0502201)the National Natural Science Foundation of China(81571550,81671613)+2 种基金the Natural Science Foundation of Zhejiang Province(LY18H100001,LY15H100001)the‘Double First-rate’project initiatives,the Shanghai Key Laboratory of Cell Engineering(14DZ2272300)the Shanghai Leading Academic Discipline Project(B905).
文摘Interleukin 17(IL-17)is an important cytokine that can induce tissue inflammation and is involved in the pathogenesis of numerous autoimmune diseases.However,the regulation of its signaling transduction has not been well described.In this study,we report that thousand and one kinase 1(TAOK1)functions as a negative regulator of IL-17-mediated signal transduction and inflammation.TAOK1 knockdown promotes IL-17-induced cytokine and chemokine expression and the activation of mitogen-activated protein kinases and nuclear factor-κB.We further demonstrate that TAOK1 interacts with IL-17 receptor A(IL-17RA)independent of its kinase activity,and TAOK1 dose-dependently prevents the formation of the IL-17R-Act1(nuclear factor activator 1,also known as tumor necrosis factor receptor-associated factor 3 interacting protein 2)complex.Consistent with this,TAOK1 deficiency exacerbates colitis in the 2,4,6-trinitrobenzenesulfonic acid-induced experimental model of inflammatory bowel disease,likely by its promotion of the IL-17-mediated signaling pathway.TAOK1 expression is decreased in the colons of ulcerative colitis patients.In conclusion,these findings suggest that TAOK1 is involved in the development of IL-17-related autoimmune disorders.
文摘Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.
