Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.

Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Research Abstract Details 

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Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Abstract Text:

Dan A Dixon,Neal D Tolley,Kristi Bemis-Standoli,Mark L Martinez,Andrew S Weyrich,Jason D Morrow,Stephen M Prescott,Guy A Zimmerman,

Tight regulation of COX-2 expression is a key feature controlling eicosanoid production in atherosclerosis and other inflammatory syndromes. Adhesive interactions between platelets and monocytes occur in these conditions and deliver specific signals that trigger inflammatory gene expression. Using a cellular model of monocyte signaling induced by activated human platelets, we identified the central posttranscriptional mechanisms that regulate timing and magnitude of COX-2 expression. Tethering of monocytes to platelets and to purified P-selectin, a key adhesion molecule displayed by activated platelets, induces NF-kappaB activation and COX-2 promoter activity. Nevertheless, COX-2 mRNA is rapidly degraded, leading to aborted protein synthesis. Time-dependent signaling of monocytes induces a second phase of transcript accumulation accompanied by COX-2 enzyme synthesis and eicosanoid production. Here, generation of IL-1beta, a proinflammatory cytokine, promoted stabilization of COX-2 mRNA by silencing of the AU-rich mRNA decay element (ARE) in the 3'-untranslated region (3'UTR) of the mRNA. Consistent with observed mRNA stabilization, activated platelets or IL-1beta treatment induced cytoplasmic accumulation and enhanced ARE binding of the mRNA stability factor HuR in monocytes. These findings demonstrate that activated platelets induce COX-2 synthesis in monocytes by combinatorial signaling to transcriptional and posttranscriptional checkpoints. These checkpoints may be altered in disease and therefore useful as targets for antiinflammatory intervention.

Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Publishing Authors By Initials

DA Dixon,ND Tolley,K Bemis-Standoli,ML Martinez,AS Weyrich,JD Morrow,SM Prescott,GA Zimmerman,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: mitogen-activated protein kinases: p38 mitogen-activated protein kinases research

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Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 116

Page Numbers: 2727-38

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 21

MONTH: 09

YEAR: 2006

Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Keywords Mesh Terms:

KEYWORDS: p38 Mitogen-Activated Protein Kinases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. Information

Substance Name: Thrombin

Registry Number: EC 3.4.21.5

Grant and Affiliation Information for Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.

AFFILIATION: Department of Biological Sciences and South Carolina Cancer Center, University of South Carolina, Columbia, South Carolina 29203, USA. ddixon@biol.sc.edu

Country: United States

AGENCY: United States NCRR

GRANT: P20RR17698

ACRONYM: RR

MEDLINETA: J Clin Invest

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