Expression of TREM-1 is inhibited by PGD2 and PGJ2 in macrophages.
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.
Syed
Mansoor Ali
MA
Department of Veterans Affairs, Jesse Brown VA Hospital, University of Illinois at Chicago, Chicago, IL, USA.
Joo
M
M
Abbas
Zulfiqar
Z
Rodger
D
D
Christman
J W
JW
Mehta
D
D
Sadikot
R T
RT
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D047495:PPAR gamma; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D051996:Transcription Factor RelA; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2