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The role of Toll-like receptor 4 on inflammation and Aβ formation in cortex astrocytes

GONG Chang-Yin, ZHOU Ai-Ling, MAO Jia-Hui, HU Ya-E, GENG Jin-Song

Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, China； Department of Pathology, Affiliated Changzhou No. 2 People’s Hospital, Nanjing Medical University, Changzhou 213003, China； Evidence-based Medicine Center, Medical School of Nantong University, Nantong 226001, China

Abstract

To investigate the role and possible molecular mechanism of astrocytes in inflammation and amyloid β-protein (Aβ) formation, in this research, by using LPS to stimulate cultured rat astrocytes in vitro with or without anti-Toll-like receptor 4 (TLR4) antibody pretreatment, we first detected the TLR4, TNF-α, IL-1β, β-amyloid precursor protein (β-APP) and β-site APP clearing enzyme 1 (BACE1) mRNA with real-time PCR, and TLR4, NF-κB/P65 protein in cultured astrocytes by Western blot, and then further probed the translocation of NF-κB/P65 using immunofluorescence and the contents of TNF-α, IL-1β and Aβ in culture supernatant through ELISA. We found that all of these indexes increased at different degrees after LPS-stimulation. However, if pretreatment with anti- TLR4 antibody, such stimulating effects of LPS on the nuclear translocation of NF-κB/P65 and TNF-α, IL-1β, Aβ contents in astrocytic culture supernatant were reduced significantly or disappeared in comparison with the group with only LPS-administration. Our results suggest that TLR4 in astrocytes might play an important role in the inflammation and Aβ formation through the TLR4/NF-κB signaling pathway, thus providing new knowledge and understanding of the inflammatory hypothesis of AD pathogenesis.

Key words: Alzheimer’s disease; astrocytes; Toll-like receptor 4; inflammation; β-amyloid protein

Received: 2014-04-29　　Accepted: 2014-07-02

Corresponding author: 周爱玲　　E-mail: alz@ntu.edu.cn

Citing This Article：

GONG Chang-Yin, ZHOU Ai-Ling, MAO Jia-Hui, HU Ya-E, GENG Jin-Song. The role of Toll-like receptor 4 on inflammation and Aβ formation in cortex astrocytes. Acta Physiol Sin 2014; 66 (6): 631-638 (in Chinese with English abstract).