TY - JOUR
T1 - TRIL, a functional component of the TLR4 signaling complex, highly expressed in brain
AU - Carpenter, Susan
AU - Carlson, Thaddeus
AU - Dellacasagrande, Jerome
AU - Garcia, Amaya
AU - Gibbons, Sharon
AU - Hertzog, Paul
AU - Lyons, Anthony
AU - Lin, Lih Ling
AU - Lynch, Marina
AU - Monie, Tom
AU - Murphy, Caroline
AU - Seidl, Katherine J.
AU - Wells, Christine
AU - Dunne, Aisling
AU - O'Neill, Luke A.J.
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349336164&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0901518
DO - 10.4049/jimmunol.0901518
M3 - Article
SN - 0022-1767
VL - 183
SP - 3989
EP - 3995
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -