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research
Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis
Authors
A Poltorak
A Wenzel
+88 more
Abigail S. Hackam
AK Silva
AL Kindzelskii
Amit K. Patel
AO Edwards
AS Hackam
B Marsh
BJ Marsh
BJ Marsh
C Bowes
C Liu
C Niehrs
C Zhang
Chhinder P. Sodhi
CP Sodhi
CY Logan
D Jiang
David J. Hackam
DJ Kaczorowski
E Cario
E Chaum
E Okun
F Hua
F Limana
G Faraco
G Tezel
GA Limb
GM Seigel
GR Barile
GS Hageman
GT Higgins
H Yi
H Yi
HL Rosenzweig
HL Rosenzweig
HP Scholl
Hyun Yi
IA El-Ghrably
J Merenmies
J Qiu
J Watson
JK Shen
JR Caso
K Hoshino
K Kaarniranta
K Miyake
K Takeda
KP Mollen
L Barandon
L Minghetti
M Mizukami
MA Fragoso
Mauricio Martins Rodrigues
MD Gordon
MK Ko
MT Lotze
N Arimura
P Matzinger
PJ Franco
PY Leung
Q Xing
R Gauthier
R Gorina
R Kacimi
R Seitz
R Shechter
RM Vabulas
RR Caspi
RT Moon
S Lehnardt
S Lin
S Tell
S Walter
S Zareparsi
SC Gribar
SC Tang
SC Tang
SR Coats
T Ha
T Harada
T Harada
T Nakazawa
U Kilic
V Bocchini
V Fontaine
Y de Kozak
Y Xin
Z Tu
Publication date
17 May 2012
Publisher
'Public Library of Science (PLoS)'
Doi
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on
PubMed
Abstract
Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al
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