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- Title
Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells.
- Authors
Prüfer, Steve; Weber, Michael; Sasca, Daniel; Teschner, Daniel; Wölfel, Catherine; Stein, Pamela; Stassen, Michael; Schild, Hansjörg; Radsak, Markus P.
- 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 Ca2+ 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 Ca2+ 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. © 2013 S. Karger AG, Basel
- Publication
Journal of Innate Immunity, 2014, Vol 6, Issue 3, p339
- ISSN
1662-811X
- Publication type
Article
- DOI
10.1159/000355892