title: Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages.
abstract: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that is expressed on the cell surface of monocytes and neutrophils. Engagement of TREM-1 triggers synthesis of proinflammatory cytokines in response to microbes, but the extent and mechanism by which TREM-1 modulates the inflammatory response is poorly defined. In the present study, we investigated the functional effects of blocking TREM-1 on the Toll-like receptor (TLR)4-mediated signaling pathway in macrophages. By transfecting cells with small hairpin interfering RNA molecules to TREM-1 (shRNA), we confirmed that TREM-1 mRNA and protein expression was greatly attenuated in RAW cells in response to treatment with LPS. PCR array for genes related to or activated by the TLR pathway revealed that although the expression of TLR4 itself was not significantly altered by silencing of TREM-1, expression of several genes, including MyD88, CD14, IkappaBalpha, IL-1beta, MCP-1, and IL-10 was significantly attenuated in the TREM-1 knockdown cells in response to treatment with LPS. These data indicate that expression of TREM-1 modulates the TLR signaling in macrophages by altering the expression of both adaptor and effector proteins that are critical to the endotoxin response.
authors: Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois, Chicago, IL 60612, USA.
authors: M
authors: M
authors: Ornatowska
authors: A C
authors: AC
authors: Azim
authors: X
authors: X
authors: Wang
authors: J W
authors: JW
authors: Christman
authors: L
authors: L
authors: Xiao
authors: M
authors: M
authors: Joo
authors: R T
authors: RT
authors: Sadikot
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D023281:Genomics; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000073871:Triggering Receptor Expressed on Myeloid Cells-1