CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells.
The CCAAT/enhancer binding protein delta (CEBPD, C/EBPδ, NF-IL6β) is induced in many inflammation-related diseases, suggesting that CEBPD and its downstream targets may play central roles in these conditions. Neuropathological studies show that a neuroinflammatory response parallels the early stages of Alzheimer's disease (AD). However, the precise mechanistic correlation between inflammation and AD pathogenesis remains unclear. CEBPD is upregulated in the astrocytes of AD patients. Therefore, we asked if activation of astrocytic CEBPD could contribute to AD pathogenesis. In this report, a novel role of CEBPD in attenuating macrophage-mediated phagocytosis of damaged neuron cells was found. By global gene expression profiling, we identified the inflammatory marker pentraxin-3 (PTX3, TNFAIP5, TSG-14) as a CEBPD target in astrocytes. Furthermore, we demonstrate that PTX3 participates in the attenuation of macrophage-mediated phagocytosis of damaged neuron cells. This study provides the first demonstration of a role for astrocytic CEBPD and the CEBPD-regulated molecule PTX3 in the accumulation of damaged neurons, which is a hallmark of AD pathogenesis.
Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan.
Chiung-Yuan
CY
Ko
Ling-Hua
LH
Chang
Yi-Chao
YC
Lee
Esta
E
Sterneck
Chun-Pei
CP
Cheng
Shun-Hua
SH
Chen
A-Mei
AM
Huang
Joseph T
JT
Tseng
Ju-Ming
JM
Wang
D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000099153:Pentraxins
D002097:C-Reactive Protein; D051743:CCAAT-Enhancer-Binding Protein-delta; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C497252:CEBPD protein, human