Abstract
TREM-1 is a superimmunoglobulin receptor present on neutrophils and monocytes, which plays an important role in the amplification of inflammation. The natural ligands for TREM-1 have not been identified; however, Toll-like receptor ligands are known to induce the expression of TREM-1. Blockade of TREM-1 has shown to improve survival in animal models of sepsis. In the present studies, we investigated the role of lipid mediators in the expression of TREM-1. In a macrophage cell line, we show that the expression of TREM-1 in response to LPS and bacteria Pseudomonas aeruginosa is inhibited by PGD(2) and cyclopentanone prostaglandins PGJ(2) and 15-dPGJ(2). The inhibition of TREM-1 by these prostaglandins is independent of the PGD(2) receptors and PPARγ but occurs by activation of Nrf2 and inhibition of NF-κB. Our data suggest a novel mechanism by which these prostaglandins exhibit anti-inflammatory effects and a new therapeutic approach to inhibition of TREM-1.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Gene Expression Regulation / drug effects
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects*
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Macrophages / metabolism*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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NF-E2-Related Factor 2 / metabolism
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PPAR gamma / metabolism
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Prostaglandin D2 / analogs & derivatives*
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Prostaglandin D2 / pharmacology
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Protein Transport / drug effects
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / physiology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Transcription Factor RelA / metabolism
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Triggering Receptor Expressed on Myeloid Cells-1
Substances
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15-deoxy-delta(12,14)-prostaglandin J2
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Lipopolysaccharides
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Membrane Glycoproteins
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NF-E2-Related Factor 2
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Nfe2l2 protein, mouse
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PPAR gamma
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RNA, Messenger
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Receptors, Immunologic
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TREM1 protein, mouse
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Transcription Factor RelA
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Triggering Receptor Expressed on Myeloid Cells-1
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9-deoxy-delta-9-prostaglandin D2
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Prostaglandin D2