CYTOKINE AND ADHESION MOLECULE EXPRESSION IN KAPOSI'S
CYTOKINE AND ADHESION MOLECULE EXPRESSION IN KAPOSI'S
批准号:
2101056
负责人:
MARGARET K OFFERMANN
金额:
$18.64万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-07-01 至 1997-04-30
关键词:
Kaposi's sarcoma biopsy cell adhesion molecules cell growth regulation gene expression human immunodeficiency virus human subject immunocytochemistry immunoprecipitation interleukin 1 interleukin 6 leukocytes northern blottings pathologic process tissue /cell culture transcription factor virus protein
中文摘要
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
它们的前体暴露在高水平的细胞因子和
感染性病原体的成分,如双链RNA和
脂多糖。我们假设这些药物激活了核因子-kappa-
B类转录因子,这种激活有助于
细胞黏附分子在KS细胞上的诱导表达
其前体,从而增强特定类型的粘附性
白细胞。这些药物还可以诱导KS细胞表达IL-6,
提示KS细胞表达的IL-6可能参与了
激活贴壁的白细胞。我们假设这些
白细胞提供因子,包括艾滋病毒的Tat蛋白和
更多的IL-6和肿瘤素M,是血管内皮细胞的中介物
KS的发展。尽管培养中的KS细胞保持着一种
与其他可被认为是候选细胞类型的细胞不同
前体,无论是CAM的表达还是IL-6的表达都不是结构性的
在KS细胞中,表明宿主因素是导致高
在KS皮损中的表达水平。因为核因子-kappa-B
一致的位点存在于CAMS、IL-6和
HIV,共同激活核因子-kappa-B的分子事件可能是
对于导致发展的许多变化和
KS的进展,因此可以作为临床的靶点
干预。我们已经确定了几种干扰机制
核因子-kappa-B通过这些试剂驱动的基因表达。这些实验是
旨在加深我们对CAM和IL-6调节的了解
在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
靶向核因子-γ-B样蛋白作为共同转录因子
参与这些基因的表达,可能是一种治疗方法
KS的治疗策略。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
SUBVERSION OF HOST ANTIVIRAL DEFENSES BY HHV8 VIRF
-
批准号:6513191
-
项目类别:
-
资助金额:$28.56万
-
财政年份:1998
-
负责人:MARGARET K OFFERMANN
-
依托单位:
SUBVERSION OF HOST ANTIVIRAL DEFENSES BY HHV8 VIRF
-
批准号:6376922
-
项目类别:
-
资助金额:$27.72万
-
财政年份:1998
-
负责人:MARGARET K OFFERMANN
-
依托单位:
SUBVERSION OF HOST ANTIVIRAL DEFENSES BY HHV8 VIRF
-
批准号:2896730
-
项目类别:
-
资助金额:$26.13万
-
财政年份:1998
-
负责人:MARGARET K OFFERMANN
-
依托单位:
SUBVERSION OF HOST ANTIVIRAL DEFENSES BY HHV8 VIRF
-
批准号:2717589
-
项目类别:
-
资助金额:$26.91万
-
财政年份:1998
-
负责人:MARGARET K OFFERMANN
-
依托单位:
SUBVERSION OF HOST ANTIVIRAL DEFENSES BY HHV8 VIRF
-
批准号:6173889
-
项目类别:
-
资助金额:$26.92万
-
财政年份:1998
-
负责人:MARGARET K OFFERMANN
-
依托单位:
MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSIS SARCOMA
-
批准号:2111055
-
项目类别:
-
资助金额:$21.82万
-
财政年份:1995
-
负责人:MARGARET K OFFERMANN
-
依托单位:
MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
-
批准号:2376967
-
项目类别:
-
资助金额:$21.39万
-
财政年份:1995
-
负责人:MARGARET K OFFERMANN
-
依托单位:
MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
-
批准号:2111056
-
项目类别:
-
资助金额:$20.56万
-
财政年份:1995
-
负责人:MARGARET K OFFERMANN
-
依托单位:
MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
-
批准号:2882422
-
项目类别:
-
资助金额:$23.13万
-
财政年份:1995
-
负责人:MARGARET K OFFERMANN
-
依托单位:
MOLECULAR EVENTS IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
-
批准号:2668011
-
项目类别:
-
资助金额:$22.24万
-
财政年份:1995
-
负责人:MARGARET K OFFERMANN
-
依托单位:
CYTOKINE AND ADHESION MOLECULE EXPRESSION IN KAPOSI'S
-
批准号:2101057
-
项目类别:
-
资助金额:$19.08万
-
财政年份:1994
-
负责人:MARGARET K OFFERMANN
-
依托单位:
CYTOKINE AND ADHESION MOLECULE EXPRESSION IN KAPOSIS
-
批准号:2101055
-
项目类别:
-
资助金额:$18.41万
-
财政年份:1994
-
负责人:MARGARET K OFFERMANN
-
依托单位:
HTLV TRANS ACTIVATOR GENES AND CELLULAR GENE EXPRESSION
-
批准号:3033316
-
项目类别:
-
资助金额:$3.1万
-
财政年份:1987
-
负责人:MARGARET K OFFERMANN
-
依托单位:
HTLV TRANS ACTIVATOR GENES AND CELLULAR GENE EXPRESSION
-
批准号:3033317
-
项目类别:
-
资助金额:$3.3万
-
财政年份:1987
-
负责人:MARGARET K OFFERMANN
-
依托单位:
海外基金