Abstract
Several ligands for Toll IL-1R (TIR) family are known to promote stabilization of a subset of short-lived mRNAs containing AU-rich elements (AREs) in their 3' untranslated regions. It is now evident however, that members of the TIR family may use distinct intracellular signaling pathways to achieve a spectrum of biological end points. Using human embryonic kidney 293 cells transfected to express different TIRs we now report that signals initiated through IL-1R1 or TLR4 but not TLR3 can promote the stabilization of unstable chemokine mRNAs. Similar results were obtained when signaling from endogenous receptors was examined using a mouse endothelial cell line (H5V). The ability of TIR family members to stabilize ARE-containing mRNAs results from their differential use of signaling adaptors MyD88, MyD88 adaptor-like protein, Toll receptor IFN-inducing factor (Trif), and Trif-related adaptor molecule. Overexpression of MyD88 or MyD88 adaptor-like protein was able to promote enhanced stability of ARE-containing mRNA, whereas Trif and Trif-related adaptor molecule exhibited markedly reduced capacity. Hence the ability of TIRs to signal stabilization of mRNA appears to be linked to the MyD88-dependent signaling pathway.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3' Untranslated Regions
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport / immunology
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Adaptor Proteins, Vesicular Transport / metabolism
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Adenosine / metabolism*
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Animals
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Antigens, Differentiation / immunology
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Antigens, Differentiation / metabolism
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Blotting, Western
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Cell Line
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Chemokines / biosynthesis
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Chemokines / genetics
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Humans
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In Situ Hybridization
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism*
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Myeloid Differentiation Factor 88
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RNA, Messenger*
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Receptors, Interleukin-1 / immunology
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Receptors, Interleukin-1 / metabolism*
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Receptors, Interleukin-1 Type I
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Signal Transduction / physiology
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
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Transfection
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Uridine / metabolism*
Substances
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3' Untranslated Regions
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Antigens, Differentiation
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Chemokines
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MYD88 protein, human
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Membrane Glycoproteins
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Interleukin-1
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Receptors, Interleukin-1 Type I
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TIRAP protein, human
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TLR3 protein, human
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TLR4 protein, human
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
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Adenosine
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Uridine