PMID- 12388243
OWN - NLM
STAT- MEDLINE
DCOM- 20030117
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 284
IP  - 1
DP  - 2003 Jan
TI  - Redox-regulated mechanisms of IL-4-induced MCP-1 expression in human vascular 
      endothelial cells.
PG  - H185-92
AB  - The present study focused on the molecular signaling pathways of monocyte 
      chemoattractant protein-1 (MCP-1) induction by interleukin-4 (IL-4) in human 
      umbilical vein endothelial cells (HUVEC). RT-PCR showed that MCP-1 mRNA 
      accumulation was markedly increased in IL-4-treated HUVEC in a time- and 
      dose-dependent manner. Antioxidants, such as pyrrolidine dithiocarbamate (PDTC) 
      and N-acetylcysteine (NAC), significantly inhibited IL-4-induced MCP-1 mRNA 
      expression. These effects correlated well with the PDTC-mediated inhibition of 
      MCP-1 promoter transcriptional activity observed in IL-4-treated HUVEC. 
      IL-4-induced MCP-1 gene expression was paralleled by a concomitant production of 
      MCP-1 protein. In agreement with MCP-1 gene expression, PDTC attenuated 
      IL-4-mediated induction of MCP-1 protein expression. In addition, IL-4 
      dramatically increased the transcription factor signal transducers and activators 
      of transcription 1 (STAT1) DNA binding activity, an effect that was attenuated by 
      PDTC. The role of STAT1 in the regulation of the IL-4-induced MCP-1 gene 
      expression was further confirmed in HUVEC transfected with a reporter construct 
      of the MCP-1 promoter with a mutated STAT1 binding site. These results 
      demonstrate that IL-4-dependent MCP-1 induction in HUVEC is mediated by 
      redox-regulated STAT1 activation.
FAU - Lee, Yong Woo
AU  - Lee YW
AD  - Department of Surgery, University of Kentucky Medical Center, Lexington 40536, 
      USA.
FAU - Hennig, Bernhard
AU  - Hennig B
FAU - Toborek, Michal
AU  - Toborek M
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020926
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Thiocarbamates)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 207137-56-2 (Interleukin-4)
RN  - 9007-49-2 (DNA)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Antioxidants/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - DNA/antagonists & inhibitors/metabolism
MH  - DNA-Binding Proteins/metabolism/physiology
MH  - Endothelium, Vascular/*metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Interleukin-4/*pharmacology
MH  - Oxidation-Reduction
MH  - Proline/*analogs & derivatives/pharmacology
MH  - STAT1 Transcription Factor
MH  - Thiocarbamates/pharmacology
MH  - Trans-Activators/metabolism/physiology
MH  - Transcription Factors/physiology
EDAT- 2002/10/22 04:00
MHDA- 2003/01/18 04:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2003/01/18 04:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - 00524.2002 [pii]
AID - 10.1152/ajpheart.00524.2002 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H185-92. doi: 
      10.1152/ajpheart.00524.2002. Epub 2002 Sep 26.