PMID- 23508573
OWN - NLM
STAT- MEDLINE
DCOM- 20131224
LR  - 20220410
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 19
IP  - 1
DP  - 2013 May 20
TI  - Signaling of high mobility group box 1 (HMGB1) through toll-like receptor 4 in 
      macrophages requires CD14.
PG  - 88-98
LID - 10.2119/molmed.2012.00306 [doi]
AB  - High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses 
      cytokinelike, proinflammatory properties when released extracellularly in the 
      C23-C45 disulfide form. HMGB1 also plays a key role as a mediator of acute and 
      chronic inflammation in models of sterile injury. Although HMGB1 interacts with 
      multiple pattern recognition receptors (PRRs), many of its effects in injury 
      models occur through an interaction with toll-like receptor 4 (TLR4). HMGB1 
      interacts directly with the TLR4/myeloid differentiation protein 2 (MD2) complex, 
      although the nature of this interaction remains unclear. We demonstrate that 
      optimal HMGB1-dependent TLR4 activation in vitro requires the coreceptor CD14. 
      TLR4 and MD2 are recruited into CD14-containing lipid rafts of RAW264.7 
      macrophages after stimulation with HMGB1, and TLR4 interacts closely with the 
      lipid raft protein GM1. Furthermore, we show that HMGB1 stimulates tumor necrosis 
      factor (TNF)-alpha release in WT but not in TLR4(-/-), CD14(-/-), TIR 
      domain-containing adapter-inducing interferon-beta (TRIF)(-/-) or myeloid 
      differentiation primary response protein 88 (MyD88)(-/-) macrophages. HMGB1 
      induces the release of monocyte chemotactic protein 1 (MCP-1), interferon 
      gamma-induced protein 10 (IP-10) and macrophage inflammatory protein 1alpha (MIP-1alpha) 
      in a TLR4- and CD14-dependent manner. Thus, efficient recognition of HMGB1 by the 
      TLR4/MD2 complex requires CD14.
FAU - Kim, Sodam
AU  - Kim S
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
FAU - Kim, Sun Young
AU  - Kim SY
FAU - Pribis, John P
AU  - Pribis JP
FAU - Lotze, Michael
AU  - Lotze M
FAU - Mollen, Kevin P
AU  - Mollen KP
FAU - Shapiro, Richard
AU  - Shapiro R
FAU - Loughran, Patricia
AU  - Loughran P
FAU - Scott, Melanie J
AU  - Scott MJ
FAU - Billiar, Timothy R
AU  - Billiar TR
LA  - eng
GR  - R01 GM050441/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R01GM050441/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130520
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Ly96 protein, mouse)
RN  - 0 (Lymphocyte Antigen 96)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - HEK293 Cells
MH  - HMGB1 Protein/*metabolism
MH  - Humans
MH  - Lipopolysaccharide Receptors/genetics/*metabolism
MH  - Lymphocyte Antigen 96/metabolism
MH  - Macrophages, Peritoneal/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/genetics
MH  - NF-kappa B/metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
PMC - PMC3667211
EDAT- 2013/03/20 06:00
MHDA- 2013/12/25 06:00
PMCR- 2013/03/12
CRDT- 2013/03/20 06:00
PHST- 2012/08/29 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/03/20 06:00 [entrez]
PHST- 2013/03/20 06:00 [pubmed]
PHST- 2013/12/25 06:00 [medline]
PHST- 2013/03/12 00:00 [pmc-release]
AID - molmed.2012.00306 [pii]
AID - 12_306_kim [pii]
AID - 10.2119/molmed.2012.00306 [doi]
PST - epublish
SO  - Mol Med. 2013 May 20;19(1):88-98. doi: 10.2119/molmed.2012.00306.