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• W1589389725 endingPage "2154" @default.
• W1589389725 startingPage "2148" @default.
• W1589389725 abstract "Abstract TLR signal via Toll-IL-1R (TIR) homology domain-containing adaptor proteins. One of these adaptors, Toll-IL-1R domain-containing adaptor inducing IFN-β-related adaptor molecule (TRAM), has been shown to be essential for TLR4 signaling in TRAM−/− mice and cell lines. Previously, we showed that MyD88 or Mal dominant-negative constructs did not inhibit LPS induction of cytokines in primary human M-CSF-derived macrophages. A possible explanation was redundancy of the adaptors during LPS signaling. TRAM is a suitable candidate to compensate for these adaptors. To investigate a potential role for TRAM in LPS signaling in human M-CSF-derived macrophages, we engineered an adenoviral construct expressing dominant-negative TRAM-C117H (AdTRAMdn). Synovial fibroblasts (SF) and human umbilical endothelial cells (HUVECs) were used as a nonmyeloid comparison. AdTRAMdn inhibited LPS-induced signaling in SFs and HUVECs, reducing NF-κB activation and cytokine production, but did not inhibit LPS signaling in M-CSF-derived human macrophages. Further investigation of other TLR ligands showed that AdTRAMdn was also able to inhibit signaling initiated by lipoteichoic acid, a TLR2 ligand, in SFs and HUVECs and lipoteichoic acid and macrophage-activating lipopeptide 2 signaling was also inhibited in TRAM−/− murine embryonic fibroblasts. We conclude that TRAM is an adaptor protein for both TLR4 and TLR2/6 signaling in SFs, HUVECs, and murine embryonic fibroblasts, but cannot demonstrate a role in human macrophages." @default.
• W1589389725 created "2016-06-24" @default.
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• W1589389725 date "2007-02-15" @default.
• W1589389725 modified "2023-09-28" @default.
• W1589389725 title "Selective Use of TRAM in Lipopolysaccharide (LPS) and Lipoteichoic Acid (LTA) Induced NF-κB Activation and Cytokine Production in Primary Human Cells: TRAM Is an Adaptor for LPS and LTA Signaling" @default.
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• W1589389725 doi "https://doi.org/10.4049/jimmunol.178.4.2148" @default.
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