Abstract:
:Microglia are the predominant resident immune cells of the brain and can assume a range of phenotypes. They are critical for normal brain development and function but can also contribute to many disease processes. Although they are widely studied, the transcriptional control of microglial phenotype and activation requires further research. PU.1 is a key myeloid transcription factor expressed by peripheral macrophages and rodent microglia. In this article, we report the presence of PU.1 specifically in microglia of the adult human brain and we examine its functional role in primary human microglia. Using siRNA, we achieved substantial PU.1 protein knock-down in vitro. By assessing a range of characteristic microglial proteins we found decreased viability of adult human microglia with reduced PU.1 protein expression. This observation was confirmed with PU.1 antisense DNA oligonucleotides. An important function of microglia is to clear debris by phagocytosis. We assessed the impact of loss of PU.1 on microglial phagocytosis and show that PU.1 siRNA reduces the ability of adult human microglia to phagocytose amyloid-beta1-42 peptide. These results show that PU.1 controls human microglial viability and function and suggest PU.1 as a molecular target for manipulation of human microglial phenotype.
journal_name
Gliajournal_title
Gliaauthors
Smith AM,Gibbons HM,Oldfield RL,Bergin PM,Mee EW,Faull RL,Dragunow Mdoi
10.1002/glia.22486subject
Has Abstractpub_date
2013-06-01 00:00:00pages
929-42issue
6eissn
0894-1491issn
1098-1136journal_volume
61pub_type
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