HMGB1 in inflammation

HMGB1 is a multifunctional protein with various roles in different cellular compartments. Extracellular HMGB1 is passively released from necrotic cells or actively secreted by monocytes/macrophages and dendritic cells in response to inflammatory stimuli. Passively released HMGB1 is recognized as a damage-associated molecular pattern (DAMP) and triggering inflammation by recruiting leukocytes. Actively secreted HMGB1 acts as a cytokine to activate inflammatory responses.

Neutrophils are the first leukocytes recruited to the site of inflammation for destroying pathogens. HMGB1 is required for the recruitment and the defense function of neutrophils.

● HMGB1 promotes neutrophil recruitment

HMGB1 activates vascular endothelial cells to express cell adhesion molecules (ICAM-1, VCAM-1). Neutrophils undergo capture and rolling through interaction with these cell adhesion molecules, transmigrate across the vessel, and are recruited to the site of inflammation.

● HMGB1 induces NETosis

In addition to promote neutrophil recruitment, HMGB1 also induces NETosis. NETosis is a type of cell death that is characterized by the formation of neutrophil extracellular traps (NETs), which are composed of chromatin and granule proteins. NETosis allows neutrophils to kill pathogens. However, excessive NETs result to tissue damage and participate in pathogenesis of autoimmune and inflammatory disorders such as atherosclerosis, COPD, SLE, rheumatoid arthritis.

● HMGB1 induces production of inflammatory cytokines

In monocytes/macrophages, HMGB1 binding to TLR2/4 initiates the activation of NFkB signaling, resulting in pro-inflammatory cytokine production. (Red more about pro-inflammatory cytokines and NFkB signaling)

● HMGB1 triggers pyroptosis

Pyroptosis, an inflammatory cell death, promotes a rapid clearance of pathogens by enhancing the defensive responses. As a DAMP, HMGB1 initiates the formation of NLRP3 inflammasome which contributes to maturation of inflammatory cytokines IL-1 and IL-18 and formation of GSDMD pores, resulting release of inflammatory cytokines. (Red more about Inflammasome & Pyroptosis)

arigo offers a total solution, including protein, neutralizing antibodies, and ELISA kits, to facilitate the research of HMGB1.