Research article summary (published 24 Aug 2009):

TRIL, a functional component of the TLR4 signaling complex, highly expressed in brain.

Full Abstract

TLR4 is the primary sensor of LPS. In this study, we describe for the first time TLR4 interactor with leucine-rich repeats (TRIL), which is a novel component of the TLR4 complex. TRIL is expressed in a number of tissues, most prominently in the brain but also in the spinal cord, lung, kidney, and ovary. TRIL is composed of a signal sequence, 13 leucine-rich repeats, a fibronectin domain, and a single transmembrane spanning region. TRIL is induced by LPS in the human astrocytoma cell line U373, in murine brain following i.p. injection, and in human PBMC. Endogenous TRIL interacts with TLR4 and this interaction is greatly enhanced following LPS stimulation. TRIL also interacts with the TLR4 ligand LPS. Furthermore, U373 cells stably overexpressing TRIL display enhanced cytokine production in response to LPS. Finally, knockdown of TRIL using small interfering RNA attenuates LPS signaling and cytokine production in cell lines, human PBMC, and primary murine mixed glial cells. These results demonstrate that TRIL is a novel component of the TLR4 complex which may have particular relevance for the functional role of TLR4 in the brain.

Author information

Author/s: Carpenter, Susan (S); Carlson, Thaddeus (T); Dellacasagrande, Jerome (J); Garcia, Amaya (A); Gibbons, Sharon (S); Hertzog, Paul (P); Lyons, Anthony (A); Lin, Lih-Ling (LL); Lynch, Marina (M); Monie, Tom (T); Murphy, Caroline (C); Seidl, Katherine J (KJ); Wells, Christine (C); Dunne, Aisling (A); O'Neill, Luke A J (LA);

Affiliation: School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 183 (issue 6) : pp 3989-95

Dates: Created 2009/09/03; Completed 2009/09/23;

PMID: 19710467, status: MEDLINE (last retrieval date: 9/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Astrocytoma - pathology Brain Chemistry Carrier Proteins - analysis; metabolism Cell Line, Tumor Cells, Cultured Cytokines - biosynthesis

Humans Leukocytes, Mononuclear - cytology Lipopolysaccharides - pharmacology Membrane Proteins - analysis; metabolism Mice Protein Binding Toll-Like Receptor 4 - metabolism

Associated Chemicals: Carrier Proteins (0) ; Cytokines (0) ; Lipopolysaccharides (0) ; Membrane Proteins (0) ; Tlr4 protein, mouse (0) ; Toll-Like Receptor 4 (0) ; Tril protein, mouse (0)

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