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• W2111720461 startingPage "5842" @default.
• W2111720461 abstract "The adapter protein TRIF mediates signal transduction through TLR3 and TLR4, inducing production of type I IFNs and inflammatory cytokines. The present study investigates the mechanisms by which TRIF signaling controls TNF-alpha biosynthesis. We provide evidence that, in LPS-stimulated murine dendritic cells, TRIF stimulates TNF-alpha biosynthesis selectively at the posttranscriptional level by promoting mRNA translation. In the absence of functional TRIF, the production of TNF-alpha protein was severely impaired, whereas TNF-alpha mRNA levels and stability, as well as transcriptional activity of the Tnfa gene, were not affected. Similarly, TRIF was required for production of LPS-induced TNF-alpha protein, but not of mRNA, in bone marrow-derived macrophages. In peritoneal macrophages, however, TRIF was also required for normal induction of TNF-alpha mRNA, suggesting cell type-related functions of TRIF. The influence of TRIF on dendritic cell TNF-alpha production was independent of type I IFNs. TRIF was required for prolonged activation of MAPKs in LPS-stimulated dendritic cells but was dispensable for the activation of NF-kappaB. Inhibition of late p38 activity attenuated LPS-stimulated elevation of TNF-alpha protein but not mRNA levels. The p38 effector kinase MK2 was directly activated through the TRIF pathway of TLR4. Importantly, stimulation of Mk2(-/-) cells through TLR3 or TLR4 severely impaired TNF-alpha protein production but did not affect TNF-alpha mRNA induction. Together, these results indicate that the TRIF signaling pathway promotes TNF-alpha mRNA translation through activation of the protein kinase MK2." @default.
• W2111720461 created "2016-06-24" @default.
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• W2111720461 date "2010-05-15" @default.
• W2111720461 modified "2023-09-30" @default.
• W2111720461 title "TRIF Signaling Stimulates Translation of TNF-α mRNA via Prolonged Activation of MK2" @default.
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• W2111720461 doi "https://doi.org/10.4049/jimmunol.0902456" @default.
• W2111720461 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20375303" @default.
• W2111720461 hasPublicationYear "2010" @default.
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