PLATELET REGULATION OF MONOKINE SYNTHESIS
PLATELET REGULATION OF MONOKINE SYNTHESIS
批准号:
6183743
负责人:
Andrew S Weyrich
金额:
$10.84万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-05-01 至 2002-04-30
关键词:
T lymphocyte atherosclerotic plaque biological signal transduction chemokine clinical research enzyme activity human subject immunoregulation inflammation interleukin 8 monocyte chemoattractant protein 1 monokines nuclear factor kappa beta platelet activation protein biosynthesis protein kinase selectins tumor necrosis factor alpha
中文摘要
描述:这个项目的长期目标是了解如何
英文摘要
DESCRIPTION: The long term goal of this project is to understand how
platelets regulate monocyte function. This issue is particularly
important since platelets interact with monocytes in a variety of
atherosclerotic disorders. The applicant recently demonstrated that
activated platelets, but not unstimulated platelets, induce immediate-
early (IE) gene expression in monocytes. Among the IE genes expressed,
interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were
synthesized and secreted by monocytes exposed to activated platelets.
Other IE genes, including tumor necrosis factor-2 (TNF-2), were not
generated. Initial results indicate that P-selectin and RANTES
(Regulated upon Activation Normal T Cell Expressed presumed Secreted),
two platelet-derived molecules, are required for both IL-8 and MCP-1
synthesis in monocytes through P-selectin and RANTES. Signaling in
monocytes through P-selectin and RANTES will be compared to signaling
induced by LPS, a potent monocyte agonist. In the first Specific Aim,
the applicant will further characterize how P-selectin and RANTES
regulate monokine synthesis. These studies will initially be defined
in a reduced system where different forms of purified P-selectin and
RANTES are presented to monocytes; and cellular MRNA, cellular retained
protein, and secreted protein for IL-8, MCP-1, and TNF-2 will be
measured. A more complex system involving platelet-monocyte
interactions to determine if P-selectin and RANTES are required for
monokine production will be examined. Specific Aim 3 will determine
if P-selectin and RANTES regulate NF-kappaB activity in monocytes. NF-
kappaB is a transcription factor that is required for maximal IL-8,
MCP-1, and TNF-2 synthesis, and initial results developed by the
applicant indicate that NF-kappaB, and its inhibitory factor IkappaB-2,
are activated by P-selectin and RANTES. The third Specific Aim will
determine if P-selectin and RANTES regulate p70 S6 kinase activity in
monocytes. p70 S6 kinase is known to translationally regulate many
proteins and other evidence also indicates that p70 S6 kinase can
regulate NF-kappaB family members. Initial results suggest that p70 S6
kinase activity is increased in monocytes following exposure to P-
selectin and RANTES or activated platelets. Moreover, inhibition of p70
S6 kinase activity by rapamycin attenuates MCP-1 secretion by monocytes
exposed to activated platelets. In the final Specific Aim, correlative
studies to determine if P-selectin and RANTES are localized in ruptured
carotid arterial plaques will be coordinated. Together, these results
will begin defining how activated platelets, through P-selectin and
RANTES, induce monokine synthesis.
期刊论文(5)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1111/j.1538-7836.2008.03211.x
发表时间:
2009-02
期刊:
Journal of thrombosis and haemostasis : JTH
影响因子:
--
作者:
[Weyrich AS, Schwertz H, Kraiss LW, Zimmerman GA]
通讯作者:
Zimmerman GA
Translational Control of Megakaryocyte and Platelet Gene Expression in Disease
-
批准号:10616557
-
项目类别:
-
资助金额:$71.22万
-
财政年份:2019
-
负责人:Andrew S Weyrich
-
依托单位:
Translational Control of Megakaryocyte and Platelet Gene Expression in Disease
-
批准号:10569253
-
项目类别:
-
资助金额:$73.09万
-
财政年份:2019
-
负责人:Andrew S Weyrich
-
依托单位:
2014 Hemostasis Gordon Research Conference and Gordon Research Seminar
-
批准号:8784662
-
项目类别:
-
资助金额:$1.25万
-
财政年份:2014
-
负责人:Andrew S Weyrich
-
依托单位:
Patient Enrollment and Data Analysis
-
批准号:8464249
-
项目类别:
-
资助金额:$31.89万
-
财政年份:2013
-
负责人:Andrew S Weyrich
-
依托单位:
Platelet Reprogramming in Human Obesity and Diabetes
-
批准号:8464247
-
项目类别:
-
资助金额:$62.26万
-
财政年份:2013
-
负责人:Andrew S Weyrich
-
依托单位:
Administrative
-
批准号:8391960
-
项目类别:
-
资助金额:$16.55万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Reprogrammed Platelets: Effectors of Thrombosis in Metabolic Syndromes
-
批准号:9068226
-
项目类别:
-
资助金额:$252.7万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Reprogrammed Platelets: Effectors of Thrombosis in Metabolic Syndromes
-
批准号:8464229
-
项目类别:
-
资助金额:$252.4万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Platelet Reprogramming in Human Obesity and Diabetes
-
批准号:8391959
-
项目类别:
-
资助金额:$66.61万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Reprogrammed Platelets: Effectors of Thrombosis in Metabolic Syndromes
-
批准号:8656415
-
项目类别:
-
资助金额:$261.08万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Human and Mouse Cell Isolation and Phenotyping
-
批准号:8391963
-
项目类别:
-
资助金额:$53.22万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Reprogrammed Platelets: Effectors of Thrombosis in Metabolic Syndromes
-
批准号:8250544
-
项目类别:
-
资助金额:$266.69万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
The Molecular Regulation of Platelet Reprogramming by the Metabolic Milieu
-
批准号:8391955
-
项目类别:
-
资助金额:$34.59万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Metabolic Regulation of Platelet Reprogramming
-
批准号:8391957
-
项目类别:
-
资助金额:$34.26万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
The Role of the Metabolic Milieu In Regulating Platelet Reprogramming in Humans
-
批准号:8391958
-
项目类别:
-
资助金额:$16.16万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Translational Research Skills Development Core
-
批准号:8392583
-
项目类别:
-
资助金额:$11.76万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
Patient Enrollment and Data Analysis
-
批准号:8391962
-
项目类别:
-
资助金额:$33.54万
-
财政年份:2012
-
负责人:Andrew S Weyrich
-
依托单位:
PAR-04-122 Extramural Facilities Construction Grant. "F*
-
批准号:7000557
-
项目类别:
-
资助金额:$800.0万
-
财政年份:2010
-
负责人:Andrew S Weyrich
-
依托单位:
Reverse Transcriptase Activity in Megakaryocytes and Platelets
-
批准号:7845031
-
项目类别:
-
资助金额:$18.81万
-
财政年份:2009
-
负责人:Andrew S Weyrich
-
依托单位:
Novel Thrombotic and Inflammatory Activities of Platelets in Sepsis
-
批准号:7851203
-
项目类别:
-
资助金额:$52.82万
-
财政年份:2009
-
负责人:Andrew S Weyrich
-
依托单位:
海外基金