PMID- 23628898
OWN - NLM
STAT- MEDLINE
DCOM- 20130801
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 93
IP  - 6
DP  - 2013 Jun
TI  - Immune complexes activate human endothelium involving the cell-signaling 
      HMGB1-RAGE axis in the pathogenesis of lupus vasculitis.
PG  - 626-38
LID - 10.1038/labinvest.2013.61 [doi]
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the 
      formation of immune complexes (ICs), which contain a complex mixture of 
      autoantigens nucleic acids, nucleic acids-associated proteins and corresponding 
      autoantibodies. In SLE, ICs are deposited in multiple organs. Vasculopathy and 
      vasculitis in SLE are typical complications and are associated with deposition of 
      ICs on endothelium, endothelial activation and inflammatory cell infiltration. 
      However, the effects of ICs on endothelial cells and the mechanisms involved 
      remain unclear. In this study, we have demonstrated for the first time that ICs 
      upregulated cell surface expression of the receptor for advanced glycation end 
      products (RAGE), the expression of intercellular adhesion molecule-1 (ICAM-1), 
      vascular cell adhesion molecule-1 (VCAM-1), increased the secretion of the 
      chemokines interleukin 8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), the 
      proinflammatoy cytokines interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) 
      and promoted the activation of the transcription factor NF-kappaB p65 in human 
      endothelial cells (P<0.05). ICs also increased transendothelial migration of 
      monocytes (P<0.05). One of the mechanisms underlying these activating effects of 
      ICs on human endothelial cells involves cell signaling by high-mobility group box 
      1 protein (HMGB1)-RAGE axis, as these effects can be partially blocked by HMGB1 
      A-box, soluble RAGE (sRAGE), SB203580, PD98059, Bay 117082 (P<0.05) and 
      co-treatment with these agents (P<0.05). In conclusion, ICs elicit 
      proinflammatory responses in human endothelial cells and alter their function 
      involving cellular signaling via the HMGB1-RAGE axis in the pathogenesis of SLE 
      vasculitis.
FAU - Sun, Wenping
AU  - Sun W
AD  - Central Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan 
      250021, People's Republic of China.
FAU - Jiao, Yulian
AU  - Jiao Y
FAU - Cui, Bin
AU  - Cui B
FAU - Gao, Xuejun
AU  - Gao X
FAU - Xia, Yu
AU  - Xia Y
FAU - Zhao, Yueran
AU  - Zhao Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130429
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Cytokines)
RN  - 0 (Flavonoids)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Imidazoles)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Sulfones)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Antigen-Antibody Complex/*metabolism
MH  - Cell Survival
MH  - Cytokines/metabolism
MH  - Endothelium, Vascular/*immunology/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Flavonoids
MH  - HMGB1 Protein/*metabolism
MH  - Humans
MH  - Imidazoles
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Lupus Vasculitis, Central Nervous System/*immunology
MH  - Monocytes/physiology
MH  - Nitriles
MH  - Pyridines
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic
MH  - Signal Transduction
MH  - Sulfones
MH  - Transcription Factor RelA/metabolism
MH  - Transendothelial and Transepithelial Migration
MH  - U937 Cells
MH  - Up-Regulation
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2013/05/01 06:00
MHDA- 2013/08/02 06:00
CRDT- 2013/05/01 06:00
PHST- 2013/05/01 06:00 [entrez]
PHST- 2013/05/01 06:00 [pubmed]
PHST- 2013/08/02 06:00 [medline]
AID - S0023-6837(22)00930-8 [pii]
AID - 10.1038/labinvest.2013.61 [doi]
PST - ppublish
SO  - Lab Invest. 2013 Jun;93(6):626-38. doi: 10.1038/labinvest.2013.61. Epub 2013 Apr 
      29.