PMID- 17949278
OWN - NLM
STAT- MEDLINE
DCOM- 20071207
LR  - 20211020
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 9
IP  - 11
DP  - 2007 Nov
TI  - Promoter elements responsible for antioxidant regulation of MCP-1 gene 
      expression.
PG  - 1979-89
AB  - Monocyte chemoattractant protein-1 (MCP-1) is produced by different cells in 
      response to inflammatory stimulation. In the present study, a series of human 
      MCP-1 promoter reporter genes were constructed to illustrate elements involved in 
      antioxidant dimethyl sulfoxide (DMSO) inhibition of MCP-1 gene expression. MCP-1 
      secretion and mRNA expression and transcription activity stimulated by TNF-alpha 
      or IL-1beta were significantly inhibited by 1% DMSO in alveolar type II 
      epithelial cells (A549). Deletion of -7537 to -2741 caused a 77% decrease in 
      reporter activity, but DMSO inhibition was still present. Deletion of -7537 to 
      -2616 containing the A1 NF-kappaB binding site resulted in a complete loss of 
      MCP-1 stimulation. Deletion of -2585 to -74 decreased reporter activity by 
      approximately 50%, and DMSO inhibited this induction. Deletion of -2614 to -74 
      containing the A2 NF-kappaB binding site completely abolished responses to 
      stimulation. Mutations of either of the NF-kappaB binding sites decreased 
      promoter activity, which could still be inhibited by DMSO, whereas deletion of 
      both NF-kappaB binding sites abolished induced transcriptional activity. Mutation 
      or deletion of the NF-kappaB binding sites significantly decreased or abolished 
      reporter activity in response to reactive oxygen intermediates (ROI), generated 
      by xanthine plus xanthine oxidase. In conclusion, DMSO inhibits MCP-1 gene 
      expression through both NF-kappaB binding sites located far upstream of the 
      5'-flanking region of the MCP-1 promoter.
FAU - Xing, Liyu
AU  - Xing L
AD  - Department of Pathology University of Michigan, Medical School, Ann Arbor, 
      Michigan 48109, USA.
FAU - Remick, Daniel G
AU  - Remick DG
LA  - eng
GR  - R01 GM050401/GM/NIGMS NIH HHS/United States
GR  - R01 GM050401-13/GM/NIGMS NIH HHS/United States
GR  - GM 50401/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.13.12.- (Luciferases)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/analysis/genetics/*metabolism
MH  - Dimethyl Sulfoxide/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, Reporter
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Interleukin-6/analysis/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Luciferases/metabolism
MH  - Lung/cytology
MH  - *Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2007/10/24 09:00
MHDA- 2007/12/08 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2007/12/08 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - 10.1089/ars.2007.1921 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2007 Nov;9(11):1979-89. doi: 10.1089/ars.2007.1921.