PMID- 16206198
OWN - NLM
STAT- MEDLINE
DCOM- 20060224
LR  - 20081121
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 53
IP  - 1
DP  - 2006 Jan 1
TI  - Astrocyte differentiation selectively upregulates CCL2/monocyte chemoattractant 
      protein-1 in cultured human brain-derived progenitor cells.
PG  - 81-91
AB  - Chemokines (chemoattractant cytokines) and their receptors are present in the 
      brain and may play roles in both neurodevelopment and neuropathology. Increased 
      brain levels of monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, 
      are found in patients with human immunodeficiency virus type 1 (HIV-1)-associated 
      dementia and other acute and chronic neurologic diseases. Although the function 
      of CCL2 in the brain is unclear, it is believed that upregulation of this 
      chemokine during neuropathologic or neuroinflammatory conditions leads to 
      recruitment of activated monocytes into the brain, where they differentiate into 
      macrophages producing neurotoxic and inflammatory molecules. We recently showed 
      that human fetal brain-derived progenitor cells are susceptible to HIV-1 and JC 
      virus infection, and that differentiation toward an astrocyte phenotype increased 
      virus production from these cells. In the current study, we found that in the 
      absence of infection, progenitors produced moderate levels of CCL2 (5.6 ng per 
      million cells). Astrocyte differentiation over 3 weeks increased CCL2 protein 
      levels 30-fold in a biphasic manner, whereas neuronal differentiation decreased 
      production 20-fold. Electromobility shift assays (EMSAs) demonstrated increased 
      nuclear NF-kappaB levels within 2 h of initiating astrocyte differentiation, and 
      inhibitors of NF-kappaB activation partially blocked the CCL2 increase in 
      differentiating astrocytes. Transfection of progenitors with mutated CCL2 
      promoter/CAT reporter constructs showed that the distal promoter region, 
      containing NF-kappaB and NF-I binding sites, is important for 
      differentiation-induced CCL2 upregulation. Together these results suggest that 
      the transcription factor NF-kappaB, and possibly NF-I, contribute to the 
      upregulation of CCL2 chemokine production during the differentiation of human 
      progenitor cells toward an astrocyte phenotype.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Lawrence, Diane M P
AU  - Lawrence DM
AD  - Laboratory of Molecular Medicine and Neuroscience, National Institute of 
      Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 
      20892, USA.
FAU - Seth, Pankaj
AU  - Seth P
FAU - Durham, Linda
AU  - Durham L
FAU - Diaz, Frank
AU  - Diaz F
FAU - Boursiquot, Roosevelt
AU  - Boursiquot R
FAU - Ransohoff, Richard M
AU  - Ransohoff RM
FAU - Major, Eugene O
AU  - Major EO
LA  - eng
GR  - R01 NS32151/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (NFI Transcription Factors)
SB  - IM
MH  - AIDS Dementia Complex/immunology/metabolism/physiopathology
MH  - Astrocytes/cytology/immunology/*metabolism
MH  - Binding Sites/physiology
MH  - Cell Differentiation/genetics/*immunology
MH  - Cells, Cultured
MH  - Central Nervous System/cytology/*embryology/metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemotaxis/genetics/immunology
MH  - HIV-1/immunology/metabolism
MH  - Humans
MH  - JC Virus/immunology/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - NFI Transcription Factors/genetics/metabolism
MH  - Phenotype
MH  - Polyomavirus Infections/immunology/metabolism/physiopathology
MH  - Promoter Regions, Genetic/genetics
MH  - Stem Cells/cytology/immunology/*metabolism
MH  - Transcriptional Activation/physiology
MH  - Tumor Virus Infections/immunology/metabolism/physiopathology
MH  - Up-Regulation/genetics/*immunology
EDAT- 2005/10/06 09:00
MHDA- 2006/02/25 09:00
CRDT- 2005/10/06 09:00
PHST- 2005/10/06 09:00 [pubmed]
PHST- 2006/02/25 09:00 [medline]
PHST- 2005/10/06 09:00 [entrez]
AID - 10.1002/glia.20261 [doi]
PST - ppublish
SO  - Glia. 2006 Jan 1;53(1):81-91. doi: 10.1002/glia.20261.