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Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Yi, H and Patel, AK and Sodhi, CP and Hackam, DJ and Hackam, AS (2012) Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis. PLoS ONE, 7 (5).

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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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yi, H
Patel, AK
Sodhi, CP
Hackam, DJ
Hackam, AS
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMartins Rodrigues, MauricioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 17 May 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0036560
Schools and Programs: School of Medicine > Surgery
Refereed: Yes
MeSH Headings: Animals; Apoptosis--physiology; Mice; Photoreceptor Cells, Vertebrate--physiology; Signal Transduction--physiology; Toll-Like Receptor 4--physiology; Wnt Proteins--metabolism
Other ID: NLM PMC3355158
PubMed Central ID: PMC3355158
PubMed ID: 22615780
Date Deposited: 04 Oct 2012 14:15
Last Modified: 20 Dec 2018 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/15569

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