title: Distinct signaling cascades of TREM-1, TLR and NLR in neutrophils and monocytic cells.
abstract: Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca(2+) mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR and NLR cascade in MUTZ-3 cells as well as primary monocytes or PMN by Western blot analysis. These studies confirmed the essential role of phosphatidyl inositide 3-kinase (PI3K) and p38MAPK in the TREM-1 as well as the TLR or NLR cascade of monocytic cells. Importantly, PI3K and p38MAPK signals in monocytic cells both control Ca(2+) mobilization and are directly connected in the TREM-1 signaling hierarchy, which contrasts previous results obtained in PMN. Taken together, our results indicate cell type-specific differences in the TREM-1 signaling cascade and contribute to an enhanced understanding of the regulation of innate inflammatory responses.
authors.affiliation: Institute for Immunology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Steve
authors.initials: S
authors.lastname: Prüfer
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Daniel
authors.initials: D
authors.lastname: Sasca
authors.forename: Daniel
authors.initials: D
authors.lastname: Teschner
authors.forename: Catherine
authors.initials: C
authors.lastname: Wölfel
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
mesh_terms: D020013:Calcium Signaling; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases