2. Academic Validation
  3. TLR4 signaling pathway mediates the LPS/ischemia-induced expression of monocytechemotactic protein-induced protein 1 in microglia

TLR4 signaling pathway mediates the LPS/ischemia-induced expression of monocytechemotactic protein-induced protein 1 in microglia

  • Neurosci Lett. 2018 Nov 1;686:33-40. doi: 10.1016/j.neulet.2018.08.052.
Shumin Chen 1,  Chenfei Lyu 1,  Junming Zhou 2,  Shaofei Huang 3,  Yongfang Zhang 1,  Guanghui Liu 1,  Kewei Liu 1,  Danqi Chen 1,  Yafang Hu 1,  Liang Zhou 4,  Yong Gu 5
Affiliations

Affiliations

  • 1 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
  • 2 Department of Continuing Education Management, The First People Hospital of Foshan, Affiliated Hospital of Sun Yat-Sen University, Foshan, Guangdong 528000, PR China.
  • 3 Department of Neurology, Guangdong General Hospital's Nanhai Hospital, Foshan, Guangdong 528200, PR China.
  • 4 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China. Electronic address: zhouliang_1963@126.com.
  • 5 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China; Department of Encephalopathy, Hainan Province Hospital of Traditional Chinese Medicine, Haikou, Hainan 570203, PR China. Electronic address: yonggu@smu.edu.cn.
PMID: 30179651 DOI: 10.1016/j.neulet.2018.08.052
Abstract

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.

Keywords

Brain ischemia; LPS; MCPIP1; Microglia; Neuroinflammation; TLR4.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z