High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease

Table 1 Actions mediated by extracellular high-mobility group box protein 1 (HMGB1)

Target cells	Biological actions of HMGB1
Dendritic cells	Maturation and capacity to home to lymph nodes.
Monocytes/macrophages	Potential proinflammatory cytokine production in collaboration with PAMP or DAMP molecules.
	Induction of MMPs.
	Promotes migration of monocytes.
Neutrophils	Enhances chemotaxis.
	Prevents apoptosis.
T lymphocytes	Proliferation and polarization toward TH1.
B lymphocytes	Potentiates activation by DNA-IgG complexes.
Epithelial cells	Increased enterocyte permeability causing barrier dysfunction.
	Bactericidal effects.
Platelets	Expressed on cell surface by activated platelets.
Osteoclasts	Enhances osteoclast formation and TNF release by direct binding to the TNF promoter.
Endothelial cells	Proangiogenic.
	Upregulation of adhesion molecules.
Smooth muscle cells	Causes migration and proliferation.
Neurons	Induces neurite outgrowth.
Astrocytes	Proinflammatory activity, including chemotactic signals and MMP formation.
	Induces glutamate release.
Cardiac myocytes	Negative inotropic effects.
	Involved in repair.
Stem cells	Chemotaxis.
	Promotes differentiation.
Tumor cells	Enhances invasiveness.
	MMP formation.
	Strong HMGB1 overexpression.

DAMP, damage-associated molecular pattern; MMP, matrix metalloproteinase; PAMP, pathogen-associated molecular pattern; TNF, tumor necrosis factor; VDJ, variable diversity joining.

ISSN: 1478-6362