The role of Toll-like receptor 4 on inflammation and Aβ formation in cortex astrocytes.
- Author:
Chang-Yin GONG
1
,
2
,
3
;
Ai-Ling ZHOU
;
Jia-Hui MAO
;
Ya-E HU
;
Jin-Song GENG
Author Information
1. Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, China
2. Department of Pathology, Affiliated Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou 213003, China
3. Evidence-based Medicine Center, Medical School of Nantong University, Nantong 226001, China. alz@ntu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Amyloid Precursor Protein Secretases;
metabolism;
Amyloid beta-Protein Precursor;
metabolism;
Animals;
Aspartic Acid Endopeptidases;
metabolism;
Astrocytes;
metabolism;
Cells, Cultured;
Cerebral Cortex;
cytology;
Inflammation;
metabolism;
Interleukin-1beta;
metabolism;
RNA, Messenger;
Rats;
Real-Time Polymerase Chain Reaction;
Signal Transduction;
Toll-Like Receptor 4;
metabolism;
Transcription Factor RelA;
metabolism;
Tumor Necrosis Factor-alpha;
metabolism
- From:
Acta Physiologica Sinica
2014;66(6):631-638
- CountryChina
- Language:English
-
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.
