Leukocyte Integrin Mac-1 Recruits Toll/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-&kgr;B Activity
作者:
Can Shi,
Xiaobin Zhang,
Zhiping Chen,
Martyn Robinson,
Daniel Simon,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2001)
卷期:
Volume 89,
issue 10
页码: 859-865
ISSN:0009-7330
年代: 2001
出版商: OVID
关键词: leukocytes;integrins;signal transduction;gene expression
数据来源: OVID
摘要:
The leukocyte integrin Mac-1 (&agr;M&bgr;2, CD11b/CD18) regulates important cell functions in inflammation, including adhesion, phagocytosis, and oxidative burst. Deficiency of Mac-1 reduces vessel wall inflammation and neointimal thickening after murine carotid artery injury. Although Mac-1 has been implicated in modulating AP-1 and NF-&kgr;B activity, the signal transduction pathways involved are undefined. cDNA array analysis of Mac-1–clustered compared with –nonclustered monocytic THP-1 cells showed increased expression of the signal transducer TRAF6 (TNF receptor–associated factor 6), leading us to consider the possibility that Mac-1 used a Toll/IL-1 receptor family–like signaling pathway. Mac-1–dependent activation of NF-&kgr;B was potentiated by wild-type, and attenuated by dominant negative, TRAF6- and TGF-&bgr;–activated kinase (TAK1) constructs. IRAK1 (IL-1 receptor associated kinase), a kinase immediately upstream of TRAF6, coimmunoprecipitated with Mac-1. Taken together, these observations indicate that Mac-1 recruits a Toll/IL-1 receptor family–like cascade to modulate NF-&kgr;B activity. This represents a new pathway for integrin-dependent modulation of gene expression.
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