HMGB1 release from cells

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that under normal conditions binds and bends DNA and facilitates gene transcription. In response to infection or injury, HMGB1 is actively secreted by innate immune cells and/or released passively by necrotic or damaged cells to function as an alarmin (Andersson U et al. 2000; Scaffidi P et al. 2002; Bonaldi T et al. 2003; Chen G et al. 2004; Lamkanfi M et al. 2010; Beyer C et al. 2012; Yang H et al. 2013). Earlier studies reported that HMGB1 did not diffuse out of cells undergoing apoptosis as HMGB1 was found to be tightly associated with the chromatin in apoptotic cells, even when the cell membrane was permeabilized artificially with detergents (Scaffidi P et al. 2002). This finding is in agreement with the general observation that apoptosis does not promote inflammation. However, further work showed that cells that undergo apoptosis do release HMGB1 (Bell CW et al. 2006; Yamada Y et al. 2011; Spencer DM et al. 2014). In human apoptotic cells (acute myeloid leukemia H60, HeLa, Jurkat T lymphocyte, pancreatic carcinoma PANC1 cell lines) HMGB1 was found to translocate into membrane-bound vesicles which are generated and released by cells during apoptosis (Spencer DM et al. 2014; Schiller M et al 2013). Outside the cell, HMGB1 can serve as an alarmin to activate innate immune responses including chemotaxis and cytokine release in both normal and aberrant immunity (Andersson U et al. 2000; Zetterström CK et al. 2002; Voll RE et al. 2008; Harris HE et al. 2012; Diener KR et al. 2013; Yang H et al. 2013).
Literature References
PubMed ID Title Journal Year
23446148 The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis

Andersson, U, Antoine, DJ, Tracey, KJ, Yang, H

J. Leukoc. Biol. 2013
16855214 The extracellular release of HMGB1 during apoptotic cell death

Bell, CW, Pisetsky, DS, Jiang, W, Reich, CF

Am. J. Physiol., Cell Physiol. 2006
12110890 Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

Bianchi, ME, Misteli, T, Scaffidi, P

Nature 2002
22344226 The extracellular release of DNA and HMGB1 from Jurkat T cells during in vitro necrotic cell death

Giessl, A, Pisetsky, DS, Distler, JH, Schett, G, Stearns, NA, Beyer, C

Innate Immun 2012
This event is regulated
Orthologous Events
Cite Us!