TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain

Carpenter, Susan, Carlson, Thaddeus, Dellacasagrande, Jerome, Garcia, Amaya, Gibbons, Sharon, Hertzog, Paul, Lyons, Anthony, Lin, Lih Ling, Lynch, Marina, Monie, Tom, Murphy, Caroline, Seidl, Katherine J., Wells, Christine, Dunne, Aisling and O'Neill, Luke A. J. (2009) TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain. Journal of Immunology, 183 6: 3989-3995. doi:10.4049/jimmunol.0901518

Author Carpenter, Susan
Carlson, Thaddeus
Dellacasagrande, Jerome
Garcia, Amaya
Gibbons, Sharon
Hertzog, Paul
Lyons, Anthony
Lin, Lih Ling
Lynch, Marina
Monie, Tom
Murphy, Caroline
Seidl, Katherine J.
Wells, Christine
Dunne, Aisling
O'Neill, Luke A. J.
Title TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2009-09
Sub-type Article (original research)
DOI 10.4049/jimmunol.0901518
Volume 183
Issue 6
Start page 3989
End page 3995
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
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Created: Wed, 09 Mar 2011, 14:32:57 EST