PMID- 15644117
OWN - NLM
STAT- MEDLINE
DCOM- 20050301
LR  - 20220331
IS  - 0300-9475 (Print)
IS  - 0300-9475 (Linking)
VI  - 61
IP  - 1
DP  - 2005 Jan
TI  - RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent 
      macrophages.
PG  - 1-9
AB  - Abstract High-mobility group box chromosomal protein 1 (HMGB1) is a protein with 
      both intranuclear functions and extracellular cytokine-like effects. In this 
      report, we study possible candidate receptors for HMGB1 on macrophages (Mphi) and 
      define pathways activated by HMGB1 binding. Bone marrow Mphi were prepared from 
      Dark Agouti (DA) rats and stimulated in vitro with HMGB1. The kinetics of tumour 
      necrosis factor (TNF) production, NO production, activation of p38 
      mitogen-activated protein kinase (MAPK), p44/42 MAPK- and SAPK/JNK-signalling 
      pathways, nuclear translocation of nuclear factor kappa B (NF-kappaB) and 
      HMGB1-induced upregulation of major histocompatibility complex (MHC) class II and 
      CD86 were analysed. Mphi from interleukin (IL)-1 receptor type I-/-, Toll-like 
      receptor 2 (TLR2-/-) and RAGE-/- mice were used to investigate the role of these 
      receptors in HMGB1 signalling. HMGB1 induced TNF and NO production by Mphi, 
      phosphorylation of all investigated MAP kinase pathways and NF-kappaB 
      translocation, and expression of MHC class II was increased. Mphi from RAGE-/- 
      mice produced significantly lower amounts of TNF, IL-1beta and IL-6, while 
      IL-1RI-/- and TLR2-/- Mphi produced cytokine levels comparable with wildtype 
      controls in response to HMGB1 stimulation. We conclude that HMGB1 has the 
      potential to induce a proinflammatory phenotype in Mphi, with RAGE as the major 
      activation-inducing receptor.
FAU - Kokkola, R
AU  - Kokkola R
AD  - Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Andersson, A
AU  - Andersson A
FAU - Mullins, G
AU  - Mullins G
FAU - Ostberg, T
AU  - Ostberg T
FAU - Treutiger, C-J
AU  - Treutiger CJ
FAU - Arnold, B
AU  - Arnold B
FAU - Nawroth, P
AU  - Nawroth P
FAU - Andersson, U
AU  - Andersson U
FAU - Harris, R A
AU  - Harris RA
FAU - Harris, H E
AU  - Harris HE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (High Mobility Group Proteins)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Receptors, Interleukin-1 Type I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Cytokines/biosynthesis
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - HMGB1 Protein/metabolism
MH  - High Mobility Group Proteins/metabolism/*pharmacology
MH  - Histocompatibility Antigens Class II/metabolism
MH  - In Vitro Techniques
MH  - Inflammation Mediators/*metabolism/pharmacology
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Phosphorylation
MH  - Rats
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Cell Surface/deficiency/genetics/metabolism
MH  - Receptors, Immunologic
MH  - Receptors, Interleukin-1/deficiency/genetics/metabolism
MH  - Receptors, Interleukin-1 Type I
MH  - Recombinant Proteins/metabolism/pharmacology
MH  - Repressor Proteins/metabolism/*pharmacology
MH  - Toll-Like Receptor 2
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2005/01/13 09:00
MHDA- 2005/03/02 09:00
CRDT- 2005/01/13 09:00
PHST- 2005/01/13 09:00 [pubmed]
PHST- 2005/03/02 09:00 [medline]
PHST- 2005/01/13 09:00 [entrez]
AID - SJI1534 [pii]
AID - 10.1111/j.0300-9475.2005.01534.x [doi]
PST - ppublish
SO  - Scand J Immunol. 2005 Jan;61(1):1-9. doi: 10.1111/j.0300-9475.2005.01534.x.