Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0166010
Title: Melatonin suppresses toll like receptor 4-dependent caspase-3 signaling activation coupled with reduced production of proinflammatory mediators in Hypoxic Microgli?
Authors: Yao L.
Lu P.
Ling E.-A. 
Keywords: caspase 3
inducible nitric oxide synthase
interleukin 1beta
melatonin
messenger RNA
toll like receptor 4
transcription factor RelA
tumor necrosis factor
autacoid
caspase 3
melatonin
toll like receptor 4
animal cell
animal experiment
animal model
animal tissue
antiinflammatory activity
Article
brain hypoxia
cell hypoxia
controlled study
in vitro study
microglia
newborn
newborn hypoxia
nonhuman
protein expression
rat
animal
cytology
deficiency
drug effects
enzyme activation
gene expression regulation
gene silencing
genetics
metabolism
microglia
signal transduction
Wistar rat
Animals
Caspase 3
Cell Hypoxia
Enzyme Activation
Gene Expression Regulation
Gene Knockdown Techniques
Inflammation Mediators
Melatonin
Microglia
Rats
Rats, Wistar
Signal Transduction
Toll-Like Receptor 4
Issue Date: 2016
Citation: Yao L., Lu P., Ling E.-A. (2016). Melatonin suppresses toll like receptor 4-dependent caspase-3 signaling activation coupled with reduced production of proinflammatory mediators in Hypoxic Microgli?. PLoS ONE 11 (11) : e0166010. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0166010
Rights: Attribution 4.0 International
Abstract: Microglia activation and associated inflammatory response play pivotal roles in the pathogenesis of different neurodegenerative diseases including neonatal hypoxic brain injury. Here we show that caspase3 expression was upregulated in activated microglia after hypoxic exposure, and remarkably, the cell viability remained unaffected alluding to the possibility of a non-apoptotic role of caspase3 in activated microglia. Chemical inhibition of caspase3 suppressed microglia activation as evident by an obvious reduction in expression of proinflammatory mediators and NF-KB signaling activation. Hypoxia induced caspase3 activation was TLR4 dependent as supported by the fact that caspase3 activation was hindered in cells with TLR4 knockdown. Interestingly, melatonin treatment significantly suppressed caspase3 activation. More importantly, melatonin also inhibited the increase in TLR4 protein and mRNA expression in hypoxic microglia. Inhibition of TLR4 expression by melatonin was also found in microglia of postnatal rats subjected to hypoxic exposure. Taken together, it is concluded that melatonin could inhibit TLR4 expression in hypoxic microglia followed by suppression of caspase3 activation leading to decrease in production of proinflammatory mediators. © 2016 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161546
ISSN: 19326203
DOI: 10.1371/journal.pone.0166010
Rights: Attribution 4.0 International
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This item is licensed under a Creative Commons License Creative Commons