CYTOKINE AND ADHESION MOLECULE EXPRESSION IN KAPOSI'S

我们假设由于感染和免疫失调 某些HIV感染患者经历的卡波西肉瘤（KS）细胞 它们的前体暴露于高水平的细胞因子， 感染因子的组分，如双链RNA和 脂多糖 我们假设这些药物激活NF-κ B， B样转录因子，这种激活有助于 诱导KS细胞上细胞粘附分子（CAM）的表达， 它们的前体，从而增强特定类型的 白细胞 这些相同的试剂也诱导KS细胞表达IL-6， 提示KS细胞表达的IL-6可能有助于 激活粘附的白细胞。 我们假设这些 白细胞提供因子，包括HIV的达特蛋白， 另外的IL-6和制瘤素M，作为免疫调节剂的药剂， KS的发展。尽管培养的KS细胞保持一种表型， 与可被视为候选细胞的其他细胞类型不同 前体，CAM表达和IL-6表达都不是组成型的 在KS细胞中，这表明宿主因素是导致高表达的原因。 KS病变中的表达水平。 因为NF-κ B B 在CAM、IL-6和 HIV，NF-κ-B激活的共享分子事件，可能是 这是许多导致发展的变化所必需的， KS的进展，因此可以作为临床治疗的目标。 干预 我们已经确定了几种干扰机制， NF-κ B通过这些试剂驱动基因表达。 这些实验 旨在增强我们对CAM和IL-6调节的理解 KS中的表达及其诱导的功能后果， 不同的特工 此外，我们还将探讨 靶向NF-γ-B样蛋白作为共享转录因子 参与这些基因的表达作为一种可能的治疗方法 KS的治疗策略。

We hypothesize that because of infections and immune dysregulation experienced by certain HIV-infected patients, Kaposi's sarcoma (KS) cells and their precursors are exposed to high levels of cytokines and to components of the infectious agents, such as double stranded RNA and lipopolysaccharide. We hypothesize that these agents activate NF-kappa- B-like transcription factors, and that this activation contributes to the induced expression of cellular adhesion molecules (CAMs) on KS cells and their precursors, thereby enhancing adhesion of specific types of leukocytes. These same agents also induce IL-6 expression by KS cells, suggesting that IL-6 expressed by the KS cells might contribute to activation of the adherent leukocytes. We hypothesize that these leukocytes provide factors, including the Tat protein of HIV and additional IL-6 and Oncostatin M, agents that are mediators in the development of KS. Although KS cells in culture maintain a phenotype that is distinct from other cell types that could be considered candidate precursors, neither CAM expression nor IL-6 expression is constitutive in KS cells, suggesting that host factors are responsible for the high levels of expression that occur in KS lesions. Because NF-kappa-B consensus sites exists in the regulatory regions of the CAMs, IL-6 and HIV, the shared molecule event of activation of NF-kappa-B could be necessary for many of the changes that lead to the development and progression of KS, and as such could serve as a target of clinical intervention. We have identified several mechanisms to interfere with NF-kappa-B-driven gene expression by these agents. These experiments are designed to enhance our understanding of the regulation of CAM and IL-6 expression in KS and the functional consequences of their induction by different agents. In addition, we will explore the consequences of targeting NF-gamma-B-like proteins as a shared transcription factor involved in the expression of these genes as a possible therapeutic strategy for the treatment of KS.