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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 |
Appears in Collections: | Staff Publications Elements |
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