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Date: 1 August 2010

Journal: GLIA Volume 58, Issue 10, 1 August 2010, Pages 1247-1256 , Doi: 10.1002/glia.21006

2010 | Foxp3 is a novel repressor of microglia activation…

Chung, H.-S.a, Lee, J.-H.a, Kim, H.a, Lee, H.-J.a, Kim, S.H.b, Kwon, H.-K.c, Im, S.-H.c, Bae, H.a

Abstract

Forkhead transcription factor3 (Foxp3) is critical for generating CD4 +CD25+ regulatory T cells. However, its role in microglia has not been identified. Here, we show that Foxp3 is expressed in microglia and is upregulated upon activation. In Foxp3 mutant mice (Foxp3sf), microglia release higher levels of inflammatory cytokines and mediators such as NO, MCP-1, CXCL10, and ROS upon liposaccharide treatment than the wild type, while TNF-α and IL-1β were not significantly different between wild and mutant microglial cells. In addition, Foxp3 silencing enhances inflammatory responses, suggesting that the major role of Foxp3 in microglia is that of a repressor of activation. Similarly, Foxp3 overexpression reduces inflammatory responses in microglia. We also demonstrate that Foxp3 interacts directly with NF-κB and modulates its transcriptional activities. These findings point to the importance of Foxp3 in NF-κB mediated inflammatory responses in microglia. © 2010 Wiley-Liss, Inc.


Author keywords

Chemokines; Inflammation; Nitric oxide; Nuclear factor κB


Indexed keywords

EMTREE drug terms: gamma interferon inducible protein 10; immunoglobulin enhancer binding protein; interleukin 1beta; lipopolysaccharide; monocyte chemotactic protein 1; nitric oxide; reactive oxygen metabolite; transcription factor FOXP3; tumor necrosis factor alpha

EMTREE medical terms: animal cell; animal cell culture; article; cell activation; controlled study; in vitro study; inflammation; microglia; mouse; nerve cell culture; nonhuman; priority journal; upregulation; wild type

MeSH: Active Transport, Cell Nucleus; Animals; Cell Count; Cell Line; Cells, Cultured; Cerebral Cortex; Chemokine CCL2; Chemokine CXCL10; Forkhead Transcription Factors; I-kappa B Proteins; Lipopolysaccharides; Mice; Mice, Transgenic; Microglia; NF-kappa B; Nitric Oxide; Phosphorylation; RNA, Messenger
Medline is the source for the MeSH terms of this document.


Chemicals and CAS Registry Numbers: gamma interferon inducible protein 10, 97741-20-3; nitric oxide, 10102-43-9;Ccl2 protein, mouse; Chemokine CCL2; Chemokine CXCL10; Cxcl10 protein, mouse; Forkhead Transcription Factors; Foxp3 protein, mouse; I-kappa B Proteins; Lipopolysaccharides; NF-kappa B; NF-kappaB inhibitor alpha, 139874-52-5; Nitric Oxide, 10102-43-9; RNA, Messenger


ISSN: 08941491 CODEN: GLIAESource Type: Journal Original language: English
DOI: 10.1002/glia.21006 PubMed ID: 20544860 Document Type: Article
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