CCAAT/enhancer binding protein delta (CEBPD) elevating PTX3 expression inhibits macrophage-mediated phagocytosis of dying neuron cells.

Abstract

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.

• Authors: Chiung-Yuan Ko, Ling-Hua Chang, Yi-Chao Lee, Esta Sterneck, Chun-Pei Cheng, Shun-Hua Chen, A-Mei Huang, Joseph T Tseng, Ju-Ming Wang
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 33 Issue 2 Pg. 422.e11-25 (Feb 2012) ISSN: 1558-1497 [Electronic] United States
• PMID: 21112127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• CEBPD protein, human
• Serum Amyloid P-Component
• CCAAT-Enhancer-Binding Protein-delta
• PTX3 protein
• C-Reactive Protein

Topics

• Apoptosis (physiology)
• Astrocytes (metabolism)
• C-Reactive Protein (metabolism)
• CCAAT-Enhancer-Binding Protein-delta (metabolism)
• Cell Communication (physiology)
• Cell Line
• Humans
• Macrophages (physiology)
• Neurons (cytology, metabolism)
• Phagocytosis (physiology)
• Serum Amyloid P-Component (metabolism)
• Up-Regulation (physiology)