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J Leukoc Biol. 2007 Jan;81(1):59-66. Epub 2006 Sep 11.

High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin.

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1
Laboratory of Molecular Immunoregulation, Center for Cancer Research, and Basic Research Program, Rm. 31-19/Bldg. 560, 1050 Boyles Street, Frederick, MD 21702, USA. dyang@ncifcrf.gov

Abstract

High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-alpha), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin.

PMID:
16966386
DOI:
10.1189/jlb.0306180
[Indexed for MEDLINE]
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