PMID- 15162419
OWN - NLM
STAT- MEDLINE
DCOM- 20040729
LR  - 20220331
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 34
IP  - 6
DP  - 2004 Jun
TI  - Mini-review: The nuclear protein HMGB1 as a proinflammatory mediator.
PG  - 1503-12
AB  - The intranuclear architectural protein that is termed high mobility group box 
      chromosomal protein 1 (HMGB1) was recently identified as a potent proinflammatory 
      mediator when present extracellularly. HMGB1 has been demonstrated to be a 
      long-searched-for nuclear danger signal passively released by necrotic, as 
      opposed to apoptotic, cells that will induce inflammation. Furthermore, HMGB1 can 
      also be actively secreted by stimulated macrophages or monocytes in a process 
      requiring acetylation of the molecule, which enables translocation from the 
      nucleus to secretory lysosomes. Subsequent transport out of the cells depends on 
      a secretion signal mediated by either extracellular lysophophatidyl-choline or 
      ATP. HMGB1 passively released from necrotic cells and HMGB1 actively secreted by 
      inflammatory cells are thus molecularly different. Extracellular HMGB1 acts as a 
      cytokine by signaling via the receptor for advanced glycated end-products and via 
      members of the Toll-like receptor family. The initiated inflammatory responses 
      include the production of multiple cytokines, chemoattraction of certain stem 
      cells, induction of vascular adhesion molecules and impaired function of 
      intestinal epithelial cells. Therapeutic administration of HMGB1 antagonists 
      rescues mice from lethal sepsis, even when initial treatment is delayed for 24 h 
      after the onset of infection, establishing a clinically relevant therapeutic 
      window that is significantly wider than for other known cytokines.
FAU - Erlandsson Harris, Helena
AU  - Erlandsson Harris H
AD  - Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, 
      Sweden. Helena.Erlandsson.Harris@cmm.ki.se
FAU - Andersson, Ulf
AU  - Andersson U
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (HMGB1 Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Acetylation
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cytoplasm/immunology
MH  - HMGB1 Protein/chemistry/*immunology
MH  - Humans
MH  - Inflammation/*immunology
MH  - Membrane Glycoproteins/*immunology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Necrosis
MH  - Receptors, Cell Surface/*immunology
MH  - Sepsis/immunology
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptors
RF  - 73
EDAT- 2004/05/27 05:00
MHDA- 2004/07/30 05:00
CRDT- 2004/05/27 05:00
PHST- 2004/05/27 05:00 [pubmed]
PHST- 2004/07/30 05:00 [medline]
PHST- 2004/05/27 05:00 [entrez]
AID - 10.1002/eji.200424916 [doi]
PST - ppublish
SO  - Eur J Immunol. 2004 Jun;34(6):1503-12. doi: 10.1002/eji.200424916.