Role of IL-8 in Cell Migration and Proliferation

描述(申请人摘要)：高浓度含ELR 患者样本中的趋化因子(IL-8、GRO-a)与不良相关 炎症性疾病和癌症的后果。在动物模型中阻断 IL-8在急性炎症中具有保护作用，并抑制血管生成，而 某些肿瘤的生长和转移。细胞迁移是一个主题， 在所有IL-8受体介导的事件中都是共同的，导致不同的 活体反应。中性粒细胞在急性炎症中的趋化作用主要是通过介导的 通过IL-8受体I型(CXCR1)，但CXCR2的生理作用 IL-8受体在贴壁细胞上的作用仍不清楚。两者都有 CXCR1和CXCR2在各种癌细胞上表达，如下所示 在内皮细胞上，它们的功能还远不清楚。迁徙的和 IL-8受体对内皮细胞和癌细胞的促生长作用 在体外和体内都被评估，重点是在 活生生的情况。在体外，信号转导级联导致 受体对细胞骨架反应的刺激将被解决，因为 细胞骨架改变是诱导迁移反应的前提 被IL-8感染。CXCR1和CXCR2在微血管中的作用 内皮细胞将在细胞迁移试验中和在 中性粒细胞/内皮细胞相互作用实验。最后，跟进 我们最近观察到在NIH 3T3细胞中表达的CXCR2会导致肿瘤 在裸鼠体内，CXCR2在肿瘤发生和转移中的作用将是 检查并试图通过抗体抑制来预防。

DESCRIPTION (Applicant's Abstract): High concentrations of ELR-containing chemokines (IL-8, gro-a) in patient samples have been associated with poor outcome of both inflammatory diseases and cancers. In animal models blockade of IL-8 was protective in acute inflammation and inhibited angiogenesis and the growth and metastasis of certain tumors. Cell migration is the theme that is common to all the IL-8 receptor mediated events, which result in such varied in vivo responses. Neutrophil chemotaxis in acute inflammation is mostly mediated by the IL-8 receptor type I (CXCR1), but the physiological role of the CXCR2 and the role of IL-8 receptors on adherent cells remain poorly defined. Both the CXCR1 and the CXCR2 are expressed on various cancer cells and as shown here on endothelial cells, where their function is far from clear. The migratory and growth promoting role of IL-8 receptors on endothelial and on cancer cells will be assessed in this grant both in vitro and in vivo with emphasis on the in vivo situation. In vitro the signal transduction cascade that leads from receptor stimulation to cytoskeletal responses will be addressed, since cytoskeletal changes are the prerequisite for the migratory responses induced by IL-8. Following this the role of the CXCR1 and CXCR2 on microvascular endothelial cells will be assessed in cell migration assays and in neutrophil/endothelial cell interaction experiments. Finally, following up on our recent observation that the CXCR2 expressed in NIH 3T3 cells causes tumors in nude mice the role of the CXCR2 in tumorigenesis and metastasis will be examined and sought to be prevented with antibody inhibition.