PMID- 20726986
OWN - NLM
STAT- MEDLINE
DCOM- 20110518
LR  - 20240511
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 161
IP  - 7
DP  - 2010 Dec
TI  - Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-kappaB 
      activation by disrupting lipid rafts in CD14-negative endothelial cells.
PG  - 1628-44
LID - 10.1111/j.1476-5381.2010.00993.x [doi]
AB  - BACKGROUND AND PURPOSE: Emodin [1,3,8-trihydroxy-6-methylanthraquinone] has been 
      reported to exhibit vascular anti-inflammatory properties. However, the 
      corresponding mechanisms are not well understood. The present study was designed 
      to explore the molecular target(s) of emodin in modifying lipopolysaccharide 
      (LPS)-associated signal transduction pathways in endothelial cells. EXPERIMENTAL 
      APPROACH: Cultured primary human umbilical vein endothelial cells (HUVECs; 
      passages 3-5) were pre-incubated with emodin (1-50 microg.mL(-1) ). LPS-induced 
      expression of pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6] and 
      chemokines (IL-8; CCL2/MCP-1) were determined by reverse transcription-PCR and 
      elisa. Nuclear factor-kappaB (NF-kappaB) activation, inhibitor of kappaB (IkappaB)alpha degradation 
      and Toll-like receptor-4 (TLR-4) were detected by immunocytochemistry and Western 
      blotting. Cholesterol depletion [by methyl beta-cyclodextrin (MBCD), a specific 
      cholesterol binding agent] and cholesterol replenishment were further used to 
      investigate the roles of lipid rafts in activation of HUVECs. KEY RESULTS: Emodin 
      inhibited, concentration-dependently, the expression of LPS-induced 
      pro-inflammatory cytokines (IL-1beta, IL-6) and chemokines (IL-8, CCL2) and, in 
      parallel, inhibited NF-kappaB activation and IkappaBalpha degradation in HUVECs. However, 
      emodin did not inhibit the NF-kappaB activation and IkappaBalpha degradation induced by 
      IL-1beta. The cholesterol binding agent, MBCD, inhibited LPS-induced NF-kappaB 
      activation in passaged HUVECs [which also lack the LPS receptor, membrane CD14 
      (mCD14)], showing that lipid rafts played a key role in LPS signalling in 
      mCD14-negative HUVECs. Moreover, emodin disrupted the formation of lipid rafts in 
      cell membranes by depleting cholesterol. CONCLUSIONS AND IMPLICATIONS: Lipid 
      rafts were crucial in facilitating inflammatory responses of mCD14-negative 
      HUVECs to LPS. Emodin disrupted lipid rafts through depleting cholesterol and, 
      consequently, inhibited inflammatory responses in endothelial cells.
FAU - Meng, Guoquan
AU  - Meng G
AD  - Department of Biophysics, School of Life Science and Technology, University of 
      Electronic Science and Technology of China, Chengdu, Sichuan, China.
FAU - Liu, Yiyao
AU  - Liu Y
FAU - Lou, Changchun
AU  - Lou C
FAU - Yang, Hong
AU  - Yang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (beta-Cyclodextrins)
RN  - 0 (methyl-beta-cyclodextrin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - KA46RNI6HN (Emodin)
SB  - IM
MH  - Atherosclerosis/drug therapy
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - Cytokines/metabolism
MH  - Emodin/*pharmacology
MH  - Endothelial Cells/immunology/metabolism
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Lipopolysaccharide Receptors/*analysis
MH  - Lipopolysaccharides/administration & dosage/*immunology
MH  - Membrane Microdomains/*metabolism
MH  - NF-kappa B/antagonists & inhibitors/immunology/metabolism
MH  - Signal Transduction/drug effects
MH  - beta-Cyclodextrins/metabolism/pharmacology
PMC - PMC3010572
EDAT- 2010/08/24 06:00
MHDA- 2011/05/19 06:00
PMCR- 2011/12/01
CRDT- 2010/08/24 06:00
PHST- 2010/08/24 06:00 [entrez]
PHST- 2010/08/24 06:00 [pubmed]
PHST- 2011/05/19 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - BPH993 [pii]
AID - 10.1111/j.1476-5381.2010.00993.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Dec;161(7):1628-44. doi: 10.1111/j.1476-5381.2010.00993.x.