Melatonin Suppresses Toll Like Receptor 4-Dependent Caspase-3 Signaling Activation Coupled with Reduced Production of Proinflammatory Mediators in Hypoxic Microglia

doi:10.1371/journal.pone.0166010

	Melatonin Suppresses Toll Like Receptor 4-Dependent Caspase-3 Signaling Activation Coupled with Reduced Production of Proinflammatory Mediators in Hypoxic Microglia
	Yao, Linli1,2 ; Lu, Pengfei1 ; Ling, Eng-Ang 3
	2016-11-03
发表期刊	PLOS ONE (IF:2.9[JCR-2023],3.3[5-Year])
ISSN	1932-6203
卷号	11 期号:11
发表状态	已发表
DOI	10.1371/journal.pone.0166010
摘要	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-kappa B 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.
收录类别	SCI
语种	英语
资助项目	National University of Singapore[R-181-000-140-592]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000386910000091
出版者	PUBLIC LIBRARY SCIENCE
WOS关键词	PERIVENTRICULAR WHITE-MATTER ; BRAIN-INJURY ; APOPTOSIS ; CELLS ; CYTOKINES ; PATHWAY ; RATS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1648
专题	生命科学与技术学院_PI研究组_吕鹏飞组
通讯作者	Ling, Eng-Ang
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China 3.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore, Singapore
第一作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yao, Linli,Lu, Pengfei,Ling, Eng-Ang. Melatonin Suppresses Toll Like Receptor 4-Dependent Caspase-3 Signaling Activation Coupled with Reduced Production of Proinflammatory Mediators in Hypoxic Microglia[J]. PLOS ONE,2016,11(11).
APA	Yao, Linli,Lu, Pengfei,&Ling, Eng-Ang.(2016).Melatonin Suppresses Toll Like Receptor 4-Dependent Caspase-3 Signaling Activation Coupled with Reduced Production of Proinflammatory Mediators in Hypoxic Microglia.PLOS ONE,11(11).
MLA	Yao, Linli,et al."Melatonin Suppresses Toll Like Receptor 4-Dependent Caspase-3 Signaling Activation Coupled with Reduced Production of Proinflammatory Mediators in Hypoxic Microglia".PLOS ONE 11.11(2016).