PMID- 16796861
OWN - NLM
STAT- MEDLINE
DCOM- 20080414
LR  - 20181201
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 86
IP  - 17
DP  - 2006 May 9
TI  - [High mobility group box-1 protein activates endothelial cells to produce 
      cytokines and has synergistic effect with lipopolysaccharide in inducing 
      interleukin-6 release].
PG  - 1191-5
AB  - OBJECTIVE: To observe the effects of high mobility group box 1 (HMGB1) protein on 
      the release of cytokines of human umbilic vein endothelial cells (HUVECs) and the 
      expression of interleukin-6 (IL-6) induced by lipopolysaccharide (LPS). METHODS: 
      HUVECs were cultured and then divided into the following groups. (1) Recombinant 
      HMGB1 protein of the terminal concentration of 15 ng/ml was added into the 
      culture fluid of HUVECs, 24 hours later the supernatant was collected to detect 
      the levels of granulocyte/macrophage colony stimulating factor (GM-CSF), 
      interferon-gamma (IFN-gamma), and interleukin-10, IL-12, IL-1beta, IL-2, IL-4, 
      IL-6, and IL-8, by using LiquiChip system. (2) HMGB1 protein of the terminal 
      concentrations of 3, 15, or 75 ng/ml was added into the culture fluid of the 
      HUVECs, 24 hours later the supernatants were collected to detect the level of 
      IL-6. (3) HMGB1 protein of the terminal concentration of 15 ng/ml was added into 
      the culture fluid of HUVECs, 1, 3, 6, 12, and 24 hours after the stimulation the 
      supernatant was collected to detect the level of IL-6. (4) The culture fluid of 
      HUVECs was added with HMGB1 protein of the terminal concentration of 15 ng/ml 
      and/or LPS of the concentration of 10 ng/ml, 24 hours later the supernatant was 
      collected to detect the level of IL-6. Culture fluid not added with HMGB1 protein 
      was used as control in any kind of test. RESULTS: (1) The levels of GM-CSF, 
      IFN-gamma, IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) secreted by 
      the HMGB1 stimulated HUVECs were 5, 7, 4.2, 27.8, 12.8, and 5.4 times that of 
      those control group (all P < 0.01) (2) The levels of IL-6 secreted by the HUVECs 
      stimulated with HMGB1 protein of the concentrations of 3, 15 and 75 ng/ml 
      respectively were 155 pg/ml +/- 33 pg/ml, 901 pg/ml +/- 184 pg/ml, and 1508 pg/ml 
      +/- 379 pg/ml respectively, all significantly higher than that of the control 
      group (32 pg/ml +/- 21 pg/ml, all P < 0.01). (3) Since 3 h after the stimulation 
      of HMGB1 protein the level of IL-6 began to increase gradually. 6, 12, and 24 
      hours after the stimulation the levels of IL-6 secreted by the HUVEC were 75 
      pg/ml +/- 22 pg/ml, 453 pg/ml +/- 78 pg/ml, and 901 pg/ml +/- 184 pg/ml 
      respectively, all significantly higher than that of the control group (32 pg/ml 
      +/- 21 pg/ml, all P < 0.01). (4) When the HUVECs were stimulated individually by 
      LPS (10 ng/ml) or HMGB1 (15 ng/ml), the levels of IL-6 increased to 289 pg/ml +/- 
      42 pg/ml and 901 pg/ml +/- 183.6 pg/ml respectively (both P < 0.01); when the 
      HUVECs were costimulated by LPS and HMGB1, the level of IL-6 increased to 2360 
      pg/ml +/- 299 pg/ml, which showing that there was a synergistic effect between 
      HMGB and LPS (F = 69.405, P < 0.001). CONCLUSION: HMGB1 activates HUVECs to 
      produce multiple inflammatory cytokines and induces HUVEC to secret IL-6 in a 
      dose- and time-dependent manner. HMGB1 can also act synergistically with LPS in 
      inducing IL-6 release, which may play an important role in the development of 
      sepsis.
FAU - Liu, Jing-Hua
AU  - Liu JH
AD  - Key Laboratory of Transcriptomics and Proteomics of Human Diseases of the 
      Ministry of Education of China and Key Laboratory of Proteomics of Guangdong 
      Province, Southern Medical University, Guangzhou 510515, China.
FAU - Li, Zhi-Jie
AU  - Li ZJ
FAU - Tang, Jing
AU  - Tang J
FAU - Liu, Ya-Wei
AU  - Liu YW
FAU - Zhao, Lei
AU  - Zhao L
FAU - Deng, Peng
AU  - Deng P
FAU - Jiang, Yong
AU  - Jiang Y
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Culture Media, Conditioned/metabolism
MH  - Cytokines/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - HMGB1 Protein/genetics/*pharmacology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-6/*metabolism
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Umbilical Veins/cytology
EDAT- 2006/06/27 09:00
MHDA- 2008/04/15 09:00
CRDT- 2006/06/27 09:00
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2008/04/15 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2006 May 9;86(17):1191-5.