TLR4型
TLR2型
愤怒(情绪)
信号转导
小胶质细胞
受体
p38丝裂原活化蛋白激酶
细胞生物学
磷酸化
脂多糖
炎症
缺血
MAPK/ERK通路
医学
免疫学
生物
内科学
神经科学
作者
Shumin Chen,Chenfei Lyu,Junming Zhou,Shaofei Huang,Yongfang Zhang,Guanghui Liu,Kewei Liu,Danqi Chen,Hu Y,Liang Zhou,Yong Gu
标识
DOI:10.1016/j.neulet.2018.08.052
摘要
Monocytechemotactic protein-induced protein 1 (MCPIP1), a newly recognized mRNA endonuclease, can be induced by lipopolysaccharide (LPS) and ischemic attack, then exerts a negative feedback loop against neuroinflammatory injury, but the specific underlying signaling pathway of the induction is unclear. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) signaling pathways are involved in LPS/ischemia-evoked inflammation. This study aims to explore which receptor signaling is mainly involved in the induction of MCPIP1 by LPS and ischemic attack. BV2 cells and mice were subjected to LPS stimulation or transient middle cerebral artery occlusion (MCAO) to examine the modulation of MCPIP1. Specific inhibitors for TLR4, TLR2 or RAGE were preadministered to explore the mechanisms of MCPIP1 expression. Results showed that MCPIP1 was significantly increased by LPS and ischemic stress both in vitro and in vivo in time and dose dependent manners. Inhibition of TLR4, rather than TLR2 or RAGE, downregulated the LPS/ischemia-induced expression of MCPIP1 and reduced the levels of TLR4, MyD88, phosphorylated-MAPK (p-P38), phosphorylated-IκBα (p-IκBα), as well as the translocation of NF-κB (p65). In conclusion, we firstly demonstrate that TLR4 signaling pathway, not TLR2 or RAGE, predominantly mediates the LPS/ischemia-induced expression of MCPIP1 in microglia.
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