PATHOGENESIS OF FEVER IN HUMANS
PATHOGENESIS OF FEVER IN HUMANS
批准号:
2707851
负责人:
Charles anthony Dinarello
金额:
$34.04万
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-12-01 至 1998-08-31
中文摘要
这项提议涉及到白介素1(IL-1)作为一种关键的
宿主对微生物入侵、炎症、免疫的反应
反应和损伤。IL-1是最早也是最突出的
在感染或损伤发生后合成的分子。
IL-1的S效应有很多与病理过程有关,
并且宿主具有合成、加工、
IL-1的转运和活性受到调控。这项建议
研究了这些不同的机制。实验是设计的
目的:探讨人血单核细胞产生IL-1的能力。至.为止
IL-1-β的总多聚腺苷RNA编码的5%
刺激后的单核细胞。机制控制着翻译
将这种RNA转化为IL-1蛋白,而其他机制似乎
控制将主要翻译产品处理为
具有生物活性的IL-1。转录、翻译和加工
IL-1在血液单核细胞中的表达与培养细胞中的不同
台词。因此,这些实验的重点是每一个
健康人体血液循环中产生IL-1的步骤,
在疾病中和在各种疾病修改的影响下
物质。将采用特殊方法防止
单核细胞表面黏附对IL-1转录的影响
两种新发展的IL-1-β和IL-1放射免疫分析方法
阿尔法将用于一项大型研究,以确定构成
“正常”的伊尔-1生产。免疫沉淀和
使用特异性、非交叉反应抗体的免疫荧光
将用于检测IL-1的大小和细胞定位。
IL-1的特定生物学活性与分子水平不同。
大小和结构-功能关系的研究
IL-1的提出是为了确定一个可能的活性部位(S)。
将对合成肽进行评估,并
与自然产生的单核细胞IL-1片段相关。
利用中毒性休克建立血流动力学休克动物模型
证候毒素可用来评价丹参的全身效应
IL-1及其片段和抑制其生物学活性的物质
活动。将使用两个临床模型来研究IL-1
补充鱼油对人体生殖功能的影响
饮食和血液透析。这些研究补充了基本的
IL-1产生的分子调控研究。
最后,这些研究检查了IL-1的产生和活性
在内源性放大和抑制模型中。
英文摘要
This proposal concerns interleukin-1 (IL-1) as a key mediator of
host responses to microbial invasion, inflammation, immunological
reaction and injury. IL-1 is one of the first and most prominent
molecular synthesized following the onset of infection or injury.
Many of IL-1's effects are involved with pathological processes,
and the host has mechanisms by which synthesis, processing,
transport and activities of IL-1 are regulated. This proposal
studies these various mechanisms. The experiments are designed
to explore IL-1 production from human blood monocytes. Up to
5% of the total polyadenylated RNA codes for IL-1-beta in
monocytes after stimulation. Mechanisms control the translation
of this RNA into IL-1 protein whereas other mechanisms seem to
control processing of the primary translation product into
biologically active IL-1. Transcription, translation and processing
of IL-1 are different in blood monocytes than in cultured cells
lines. Therefore, these experiments are focused on each of the
steps of IL-1 production in circulating human blood cells in health,
in disease and under the influence of various disease modifying
substances. special methods will be employed that prevent the
transcription of Il-1 in monocytes due to adherence to surfaces.
Two newly developed radioimmunoassays for IL-1-beta and Il-1-
alpha will be used in a large study to establish what constitutes
"normal" Il-1 production. Immunoprecipitation and
immunofluorescence using specific, non-cross reacting antibodies
will be used to detect the sizes and cellular localization of IL-1.
The specific biological activities of Il-1 differ with the molecular
size and hence studies on the structure-function relationship of
IL-1 are proposed in order to identify a putative active site(s).
The evaluation of synthetic peptides will be performed and
correlated with naturally occurring fragments of monocyte Il-1.
An animal model of hemodynamic shock using toxic shock
syndrome toxin is to be used to evaluate the systemic effects of
Il-1, its fragments and substances that inhibit its biological
activities. Two clinical models will be used to study Il-1
production in human subjects: the effect of supplemental fish oil
diet and hemodialysis. These studies complement the basic
investigations on the molecular control of IL-1 production.
Finally, these studies examine the production and activity of IL-1
in models of endogenous amplification and inhibition.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.3389/fimmu.2019.02632
发表时间:
2019-11
期刊:
Frontiers in Immunology
影响因子:
7.3
作者:
[S. Mountford;A. Ringleb;R. Schwaiger;D. Mayr;S. Kobold;C. Dinarello;P. Bufler]
通讯作者:
S. Mountford;A. Ringleb;R. Schwaiger;D. Mayr;S. Kobold;C. Dinarello;P. Bufler
Molecular Mechanisms of Cytokine Induced Insulin Resistance
-
批准号:9388051
-
项目类别:
-
资助金额:$20.38万
-
财政年份:2017
-
负责人:Charles anthony Dinarello
-
依托单位:
Role of Interleukin-18 in Acute Lung Injury
-
批准号:6553928
-
项目类别:
-
资助金额:$23.74万
-
财政年份:2002
-
负责人:Charles anthony Dinarello
-
依托单位:
Heterogeneous Neutrophil Responses in Acute Lung Injury
-
批准号:7095868
-
项目类别:
-
资助金额:$155.92万
-
财政年份:2002
-
负责人:Charles anthony Dinarello
-
依托单位:
Heterogeneous Neutrophil Responses in Acute Lung Injury
-
批准号:6916449
-
项目类别:
-
资助金额:$151.31万
-
财政年份:2002
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:6124162
-
项目类别:
-
资助金额:$43.77万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:6033541
-
项目类别:
-
资助金额:$42.49万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:2060259
-
项目类别:
-
资助金额:$43.07万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:3126288
-
项目类别:
-
资助金额:$21.07万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:2404924
-
项目类别:
-
资助金额:$44.73万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
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批准号:7554811
-
项目类别:
-
资助金额:$36.34万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
-
批准号:8451338
-
项目类别:
-
资助金额:$34.33万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Man
-
批准号:10492671
-
项目类别:
-
资助金额:$36.46万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENENESIS OF FEVER IN HUMANS
-
批准号:3480845
-
项目类别:
-
资助金额:$29.49万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
-
批准号:6579325
-
项目类别:
-
资助金额:$37.38万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
PATHOGENESIS OF FEVER IN HUMANS
-
批准号:6328661
-
项目类别:
-
资助金额:$45.08万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
-
批准号:6699922
-
项目类别:
-
资助金额:$37.71万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
-
批准号:8645573
-
项目类别:
-
资助金额:$36.52万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Man
-
批准号:9201590
-
项目类别:
-
资助金额:$31.1万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Humans
-
批准号:8260334
-
项目类别:
-
资助金额:$36.52万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
Pathogenesis of Fever in Man
-
批准号:10366945
-
项目类别:
-
资助金额:$37.85万
-
财政年份:1986
-
负责人:Charles anthony Dinarello
-
依托单位:
海外基金