Expression and Regulation of Inflammatory Cytokine Genes In Vitro and In Vivo

炎症细胞因子基因的体外和体内表达和调控

• 批准号: 04671366
• 负责人: KASAHARA Tadashi
• 金额: $ 1.41万
• 依托单位: Jichi Medical School, Department of Medicine Grant-in-Aid for Scientific Research(C)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671366/
• 关键词: Inflammatory cytokine; IL-8; MCAF; gene regulation; neutrophil chemotaxis; in vivo effect; 1L-8; ケモタキシス

We investigated the in vitro and in vivo role of inflammatory cytokines, IL-8 and MCAF with neutrophil and monocyte chemotactic activities, which is induced rapidly by the stimulation of IL-1 or TNF.Our results indicate that(1) Induction of IL-8 and MCAF Genes in Various Tumor Cell Lines and Its Regulation by Glucocorticoid : Fibrosarcoma and glioblastoma cell lines were found to express high levels of these inflammatory cytokines genes. The regulatory elements in IL-8 gene and nuclear factors (NF-kB, C/EBP, AP-1) were identified, particularly in interests of glucocorticoid action (Mukaida et al. Immunol.1992 ; Eur.Cytok, Netw 1993 ; J.Biol.Chem.1994 in press).(2) Determination of Inflammatory Cytokines In Various Disease States : Production of IL-8 and MCAF in various infectious and inflammatory diseases were determined using ELISA methods. Significant levels of IL-8 was observed in urines from urinary tract infection and amniotic fluids from pregnant women. Similarly, significant levels of IL-8 were detected in synovial fluids from rheumatoid arthritis or pleural fluids from cancer patients, providing valuable monitoring in these inflammatory responses.(Saito et al. Cytokine 1993 ; Ko et al. Infect. Immunity 1993 ; Tsuchiya et al.Cytokine 1993)(3) Large-scale Production of MCAF and In Vivo Application : Administration of MCAF was found to be effective to protect mice from lethal Salmonella and Pseudomonas infection in vivo (Nakano et al.Infect.Immun.1994)

我们研究了炎症细胞因子IL-8和MCAF在体外和体内的作用，这些细胞因子具有中性粒细胞和单核细胞趋化活性，通过IL-1或TNF的刺激迅速诱导。我们的结果表明：（1）各种肿瘤细胞系中IL-8和MCAF基因的诱导及其受糖皮质激素的调节：发现了纤维肉瘤和胶质母细胞瘤细胞系 表达高水平的这些炎症细胞因子基因。鉴定了 IL-8 基因和核因子（NF-kB、C/EBP、AP-1）中的调节元件，特别是糖皮质激素作用的调节元件（Mukaida 等人，Immunol.1992；Eur.Cytok，Netw 1993；J.Biol.Chem.1994，待出版）。（2）各种疾病状态下炎症细胞因子的测定：IL-8 和 IL-8 的产生MCAF 在 使用ELISA方法测定各种感染性和炎症性疾病。在尿路感染的尿液和孕妇的羊水中观察到显着水平的 IL-8。类似地，在类风湿性关节炎的滑液或癌症患者的胸膜液中检测到显着水平的 IL-8，这为这些炎症反应提供了有价值的监测。（Saito 等人 Cytokine 1993；Ko 等人 Infect.Immunity 1993；Tsuchiya 等人 Cytokine 1993）(3) MCAF 的大规模生产和体内应用：施用 MCAF 被发现可有效保护小鼠体内免受致命的沙门氏菌和假单胞菌感染（Nakano et al.Infect.Immun.1994）

项目成果

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Kikuchi,Y.: "Induction of metallothionein in a human astrocytoma cell Iine by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)

Kikuchi,Y.：“白细胞介素 1 和重金属在人星形细胞瘤细胞系中诱导金属硫蛋白。”

Morita,M.: "Induction and regulation of IL-8 and MCAF mRNAexpression in human glioblastoma and neuroblastoma cell Iines." Eur.Cytokine Netw.4. 351-358 (1993)

Morita,M.：“人胶质母细胞瘤和神经母细胞瘤细胞系中 IL-8 和 MCAF mRNA 表达的诱导和调节。”

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Ko,Y-C. Mukaida,N.Kasahara,T.et al.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human 1L-8." J.lmmunol.Methods. 149. 227-235 (1992)

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