[Triggering receptor expressed on myeloid cells-1 as an inflammation amplifier].
Triggering receptor expressed on myeloid cells (TREM)-1 is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in diseases related to bacterial infection. Its blockade suppressed fatal immune responses in mice models of sepsis without impairing the host defense. However, the influence of TREM-1 on non-bacterial diseases was not elucidated. We describe here that TREM-1 expression was up-regulated by prostaglandin (PG) E(2) as well as lipopolysaccharide. Activation of TREM-1 expressed on PGE(2)-pretreated peripheral blood mononuclear cells by an agonistic TREM-1 mAb significantly enhanced the production of TNFalpha. Indeed, monosodium urate monohydrate (MSU) crystals induced TREM-1 expression in vitro and in vivo. MSU crystals and an anti-TREM-1 agonistic antibody synergistically increased the production of interleukin-1beta compared with stimulation with the crystals alone. Furthermore, TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with collagen-induced arthritis (CIA). Blockade of TREM-1 ameliorated CIA without affecting T cell and B cell immune responses to the inducing antigen. These results provide evidence that TREM-1 may contribute the development of non-microbial inflammatory diseases through the enhancement of inflammatory responses.
Murakami
Yousuke
Y
Dearptment of Medicine and Rheumatology, Graduate school of Medicine, Tokyo Medical and Dental University.
Kohsaka
Hitoshi
H
D000818:Animals; D001168:Arthritis / Q000276:immunology; D015210:Arthritis, Gouty / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000737:chemistry*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015232:Dinoprostone