REGULATION OF HUMAN INTERLEUKIN-8 RECEPTORS
人白细胞介素 8 受体的调节
基本信息
- 批准号:2672624
- 负责人:
- 金额:$ 10.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-06-01 至 2001-05-31
- 项目状态:已结题
- 来源:
- 关键词:autoradiography cell migration chemoattractants complement receptor cytokine receptors flow cytometry human genetic material tag immunoprecipitation inflammation interleukin 8 phospholipase C phosphorylation platelet activating factor point mutation polymerase chain reaction receptor expression site directed mutagenesis tissue /cell culture
项目摘要
Interleukin-8 (IL-8) has been shown to be a key mediator of immunological
reactions in many inflammatory disorders such as respiratory distress
syndrome, idiopathic pulmonary fibrosis, rheumatoid arthritis and asthma.
As is the case for other proinflammatory mediators, phagocytic leukocytes
respond to IL-8 by migrating to sites of inflammation where they become
activated and participate in host defense. These functions are mediated
via specific cell surface receptors for IL-8. Two subtypes of IL-8
receptors (IL-8RA & IL-8RB) have been described in neutrophils. Both
subtypes of IL-8R become desensitized upon IL-8-stimulation. In addition
to homologous and heterologous desensitization, IL-8R are cross-
desensitized by other chemoattractants. To date, little is known about
the mechanism governing IL-8R regulation. Our studies have shown that IL-
8R-mediated responses are the most susceptible to cross-desensitization by
other chemoattractants in neutrophils. These studies have also indicated
that components(s) distal to the receptor/G-protein may be involved in
chemoattractant receptor cross-regulation. The main focus of the present
proposal is on the regulation of the IL-8 receptors and the mechanisms by
which they undergo desensitization and cross-desensitization. First, we
will use a rat basophilic leukemia (RBL-2H3) cell line, a functionally
responsive cell line, to stably express epitope-tagged IL-8 receptors
(ETIL-8RA and ETIL-8RB) and elucidate the role of agonist-dependent and
independent phosphorylation in the regulation of IL-8R-mediated responses.
Second, we will use directed mutagenesis and deletion to identify specific
amino acid residues of the cytoplasmic domains of the IL-8R involved in
modulating receptor functions. Third, we will determine the mechanisms of
cross-phosphorylation and desensitization between IL-8 receptors and other
chemoattractant receptors by stably coexpressing the receptors in RBL-2H3
cells. And fourth, we will determine the role of phospholipase C beta2
(PLCbeta2) in IL-8 receptor cross-regulation.
Understanding the molecular mechanisms involved in the regulation of the
IL-8R and the role played by these receptors in the cross-regulation of
chemoattractant-mediated inflammatory responses will aid in understanding
the control of inflammation as well as the etiology of many inflammatory
disorders. These studies will also identify specific targets for the
development of therapeutic drugs for the modulation of inflammation.
白细胞介素-8(IL-8)已被证明是免疫调节的关键介质。
许多炎症性疾病的反应,如呼吸窘迫
综合征、特发性肺纤维化、类风湿性关节炎和哮喘。
与其他促炎介质一样,吞噬白细胞
通过迁移到炎症部位对IL-8作出反应,
激活并参与宿主防御。 这些功能是通过
通过IL-8的特异性细胞表面受体。 IL-8的两种亚型
在嗜中性粒细胞中已经描述了IL-8受体(IL-8 RA和IL-8 RB)。 两
IL-8 R的亚型在IL-8刺激后变得脱敏。 此外
IL-8 R与同源和异源脱敏有交叉作用,
对其他化学引诱物不敏感。 到目前为止,人们对
IL-8 R调节机制。 我们的研究表明,IL-
8 R介导的反应最容易受到交叉脱敏的影响,
中性粒细胞中的其他化学引诱物。 这些研究还表明,
受体/G蛋白远端的成分可能参与
化学引诱物受体交叉调节。 目前的主要焦点
建议是关于IL-8受体的调节和机制,
他们经历了脱敏和交叉脱敏。 一是
将使用大鼠嗜碱性白血病(RBL-2 H3)细胞系,
应答细胞系,以稳定表达表位标记的IL-8受体
(ETIL-8 RA和ETIL-8 RB)的作用,并阐明激动剂依赖性和
在IL-8 R介导的应答的调节中独立的磷酸化。
第二,我们将使用定向突变和缺失来鉴定特异性
IL-8 R的胞质结构域的氨基酸残基参与
调节受体功能。 第三,我们将确定
IL-8受体和其他受体之间的交叉磷酸化和脱敏
通过在RBL-2 H3中稳定共表达受体的化学引诱物受体
细胞 第四,我们将确定磷脂酶C β 2
(PLC β 2)在IL-8受体交叉调节中的作用。
了解参与调节的分子机制,
IL-8 R及其受体在IL-8受体交叉调节中的作用
趋化因子介导的炎症反应将有助于理解
炎症的控制以及许多炎性疾病的病因
紊乱 这些研究还将确定
开发用于调节炎症的治疗药物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MICHELER Ricardo RICHARDSON其他文献
MICHELER Ricardo RICHARDSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MICHELER Ricardo RICHARDSON', 18)}}的其他基金
NCCU-LCCC Partnership in Cancer Research
NCCU-LCCC 癌症研究合作伙伴关系
- 批准号:
10247140 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partrnership in Cancer Research (1 of 2)
NCCU-LCCC 癌症研究合作伙伴关系(1 of 2)
- 批准号:
8060722 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partrnership in Cancer Research (1 of 2)
NCCU-LCCC 癌症研究合作伙伴关系(1 of 2)
- 批准号:
8332132 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partrnership in Cancer Research (1 of 2)
NCCU-LCCC 癌症研究合作伙伴关系(1 of 2)
- 批准号:
8547628 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partnership in Cancer Research
NCCU-LCCC 癌症研究合作伙伴关系
- 批准号:
9761993 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partrnership in Cancer Research (1 of 2)
NCCU-LCCC 癌症研究合作伙伴关系(1 of 2)
- 批准号:
8871990 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
NCCU-LCCC Partrnership in Cancer Research (1 of 2)
NCCU-LCCC 癌症研究合作伙伴关系(1 of 2)
- 批准号:
8729288 - 财政年份:2010
- 资助金额:
$ 10.67万 - 项目类别:
相似海外基金
RUI: Mechanoregulation of Collective Cell Migration in Biomimetic Microenvironments
RUI:仿生微环境中集体细胞迁移的机械调节
- 批准号:
2342274 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
CAREER: Predictive Multiscale Modeling of Cell Migration through Pores between Endothelial Cells
职业:通过内皮细胞之间的孔进行细胞迁移的预测多尺度建模
- 批准号:
2339054 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
Uncovering the Underlying Biophysical Mechanisms of Directed Cell Migration
揭示定向细胞迁移的潜在生物物理机制
- 批准号:
2345411 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
Collaborative Research: DMS/NIGMS 1: Simulating cell migration with a multi-scale 3D model fed by intracellular tension sensing measurements
合作研究:DMS/NIGMS 1:使用由细胞内张力传感测量提供的多尺度 3D 模型模拟细胞迁移
- 批准号:
2347957 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
Collaborative Research: DMS/NIGMS 1: Simulating cell migration with a multi-scale 3D model fed by intracellular tension sensing measurements
合作研究:DMS/NIGMS 1:使用由细胞内张力传感测量提供的多尺度 3D 模型模拟细胞迁移
- 批准号:
2347956 - 财政年份:2024
- 资助金额:
$ 10.67万 - 项目类别:
Standard Grant
Mitochondrial positioning regulates redox-signaling during cell migration
线粒体定位调节细胞迁移过程中的氧化还原信号
- 批准号:
10520211 - 财政年份:2023
- 资助金额:
$ 10.67万 - 项目类别:
Localized mitochondrial metabolic activity in Xenopus mesendoderm cells undergoing collective cell migration
爪蟾中内胚层细胞集体细胞迁移的局部线粒体代谢活性
- 批准号:
10751722 - 财政年份:2023
- 资助金额:
$ 10.67万 - 项目类别:
Full Project 1: Defining Mechanisms of MICAL-dependent Pancreatic Cancer Cell Migration
完整项目 1:MICAL 依赖性胰腺癌细胞迁移的定义机制
- 批准号:
10762273 - 财政年份:2023
- 资助金额:
$ 10.67万 - 项目类别:
Actin gating of crosstalk between Rho GTPases in cell migration
细胞迁移中 Rho GTP 酶之间串扰的肌动蛋白门控
- 批准号:
10736927 - 财政年份:2023
- 资助金额:
$ 10.67万 - 项目类别:
Mechanisms underlying a decline in neural stem cell migration during aging
衰老过程中神经干细胞迁移下降的机制
- 批准号:
10750482 - 财政年份:2023
- 资助金额:
$ 10.67万 - 项目类别: