title: MYD88-dependent and -independent activation of TREM-1 via specific TLR ligands.
abstract: Triggering receptor expressed on myeloid cells (TREM)-1 plays an important role in myeloid cell-activated inflammatory responses. Although TLR ligands such as LPS and lipoteichoic acid have been shown to upregulate TREM-1 expression in macrophage and neutrophils, the role of specific TLR in inducing the expression of TREM-1 remains unclear. In this study, we investigated whether the presence of TLR is necessary for the expression of TREM-1. We show that BM-derived macrophages from TLR4 and TLR2 KO mice failed to induce expression of TREM-1 message and protein in response to their specific ligands. Interestingly, the expression of TREM-1 in response to LPS is not altered in myeloid differentiation factor 88 (MyD88) KO macrophages, suggesting that downstream of TLR a MyD88-independent pathway induces the expression of TREM-1. Inhibiting toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) expression by siRNA decreased TREM-1 expression in response to LPS, suggesting that the expression of TREM-1 in response to LPS was mediated by the TRIF signaling pathway. On the other hand, the expression of TREM-1 in response to lipoteichoic acid is dependent on MyD88 expression. These data indicate that the expression of TREM-1 in response to TLR ligands occurs secondary to downstream signaling events and that the presence of TLR is necessary for the expression of TREM-1 in response to their specific ligands. However, the downstream signaling required for the expression of TREM-1 is dependent on the stimulus and the surface receptor through which the signaling is initiated.
authors.affiliation: Department of Veterans Affairs, Jesse Brown VA Hospital, and Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Heiderscheidt
authors.forename: Myung
authors.initials: M
authors.lastname: Joo
authors.forename: Xeipei
authors.initials: X
authors.lastname: Gao
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Knezevic
authors.forename: Dolly
authors.initials: D
authors.lastname: Mehta
authors.forename: Ruxana T
authors.initials: RT
authors.lastname: Sadikot
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013379:Substrate Specificity; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C517262:TREM1 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse