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.

Pisetsky et al. Arthritis Research & Therapy 2008 10:209   doi:10.1186/ar2440