PMID- 23037589
OWN - NLM
STAT- MEDLINE
DCOM- 20130613
LR  - 20190819
IS  - 1347-4820 (Electronic)
IS  - 1346-9843 (Linking)
VI  - 77
IP  - 1
DP  - 2013
TI  - Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte 
      chemoattractant protein-1 expression in human umbilical vein endothelial cells.
PG  - 224-30
AB  - BACKGROUND: Indoxyl sulfate (IS) is a uremic toxin that causes renal injury, but 
      little is known about its adverse effects on the cardiovascular system. The aryl 
      hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor that 
      mediates adaptive and toxic responses in cells. Recent studies identified IS as 
      an endogenous agonist for AhR, as well as other tryptophan metabolites. The aim 
      of the study was to investigate whether IS activates AhR, with subsequent 
      inflammatory responses contributing to the development of atherogenesis, in human 
      umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: We demonstrated 
      that IS stimulates the expression of AhR target genes, including cytochromes P450 
      1A1 and 1B1 mRNA, in a time-dependent manner, as well as translocation of AhR 
      into the nucleus from the cytoplasm, indicating AhR activation. IS-stimulated AhR 
      activation was accompanied by an increase in oxidative stress, proven by enhanced 
      NADPH oxidase 4 expression and dihydroethidium staining. Additionally, AhR 
      inhibitors abolished the IS-induced increase in monocyte chemoattractant 
      protein-1 (MCP-1) expression in a dose-dependent manner. Taken together, these 
      results suggest that IS activates AhR as an endogenous agonist and induces MCP-1 
      expression through reactive oxygen species production in HUVECs. CONCLUSIONS: Our 
      findings give a novel understanding of the physiological effect of IS on the 
      cardiovascular system and indicate possibilities for preventing cardiorenal 
      syndrome by regulating serum IS levels.
FAU - Watanabe, Ippei
AU  - Watanabe I
AD  - Department of Laboratory Medicine, School of Medicine, Toho University, Tokyo, 
      Japan.
FAU - Tatebe, Junko
AU  - Tatebe J
FAU - Namba, Shunji
AU  - Namba S
FAU - Koizumi, Masayuki
AU  - Koizumi M
FAU - Yamazaki, Junichi
AU  - Yamazaki J
FAU - Morita, Toshisuke
AU  - Morita T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121004
PL  - Japan
TA  - Circ J
JT  - Circulation journal : official journal of the Japanese Circulation Society
JID - 101137683
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - N187WK1Y1J (Indican)
SB  - IM
MH  - Chemokine CCL2/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*drug effects
MH  - Human Umbilical Vein Endothelial Cells/*metabolism/pathology
MH  - Humans
MH  - Indican/*toxicity
MH  - Inflammation/chemically induced/metabolism/pathology
MH  - Oxidative Stress/*drug effects
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Time Factors
EDAT- 2012/10/06 06:00
MHDA- 2013/06/14 06:00
CRDT- 2012/10/06 06:00
PHST- 2012/10/06 06:00 [entrez]
PHST- 2012/10/06 06:00 [pubmed]
PHST- 2013/06/14 06:00 [medline]
AID - DN/JST.JSTAGE/circj/CJ-12-0647 [pii]
AID - 10.1253/circj.cj-12-0647 [doi]
PST - ppublish
SO  - Circ J. 2013;77(1):224-30. doi: 10.1253/circj.cj-12-0647. Epub 2012 Oct 4.