PMID- 14736953
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20190513
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 19
IP  - 2
DP  - 2004 Feb
TI  - Dexamethasone regulates AP-1 to repress TNF-alpha induced MCP-1 production in 
      human glomerular endothelial cells.
PG  - 312-9
AB  - BACKGROUND: Glomerular endothelial cells play a role in the pathogenesis of 
      glomerulonephritis by producing chemotactic factors. We investigated the role of 
      NF-kappa B and AP-1 in tumour necrosis factor alpha (TNF-alpha) induced monocyte 
      chemoattractant protein 1 (MCP-1) production in cultured human glomerular 
      endothelial cells (HGEC). We also examined whether or not these processes could 
      be modified by glucocorticoid. METHODS: MCP-1 protein and mRNA levels were 
      measured by ELISA and northern blot. NF-kappa B and AP-1 binding activity were 
      assessed by electrophoretic mobility shift assay. Cytosolic I kappa B alpha and 
      nuclear p65 protein were evaluated by western blot. For specific inhibition of 
      NF-kappa B or AP-1, we used a decoy oligodeoxynucleotide. RESULTS: TNF-alpha (10 
      ng/ml) increased MCP-1 mRNA expression in HGEC and also the release of MCP-1 
      protein into culture media. These effects could be partially inhibited by 
      dexamethasone (10 nM). TNF-alpha induced MCP-1 production appeared to be NF-kappa 
      B and AP-1 interdependent, based on the following results. (i) TNF-alpha 
      increased NF-kappa B and AP-1 binding activity. (ii) Both NF-kappa B decoy 
      oligodeoxynucleotide and AP-1 decoy oligodeoxynucleotide partially suppressed 
      TNF-alpha induced MCP-1 mRNA expression. On the other hand, dexamethasone 
      decreased TNF-alpha induced DNA-binding activity of AP-1 without an effect on the 
      DNA-binding activity of NF-kappa B, cytosolic I kappa B alpha degradation or p65 
      nuclear translocation. CONCLUSIONS: These data demonstrate that while TNF-alpha 
      induced MCP-1 production is mediated by the cooperative action of NF-kappa B and 
      AP-1 in HGEC, dexamethasone represses TNF-alpha induced MCP-1 production via 
      suppression of AP-1 binding activity.
FAU - Park, Su-Kil
AU  - Park SK
AD  - Department of Internal Medicine, Asan Medical Center, College of Medicine, 
      University of Ulsan, Seoul, Korea. skpark@www.amc.seoul.kr
FAU - Yang, Won Seok
AU  - Yang WS
FAU - Han, Nam Jung
AU  - Han NJ
FAU - Lee, Sang Koo
AU  - Lee SK
FAU - Ahn, Hanjong
AU  - Ahn H
FAU - Lee, In Kyu
AU  - Lee IK
FAU - Park, Joong Yeol
AU  - Park JY
FAU - Lee, Ki-Up
AU  - Lee KU
FAU - Lee, Jae Dam
AU  - Lee JD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Dexamethasone/*pharmacology
MH  - Down-Regulation
MH  - Drug Interactions
MH  - Endothelium, Vascular/*cytology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Kidney Glomerulus/cytology
MH  - Molecular Sequence Data
MH  - NF-kappa B/drug effects/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Reference Values
MH  - Sensitivity and Specificity
MH  - Transcription Factor AP-1/drug effects/*metabolism
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 2004/01/23 05:00
MHDA- 2004/10/06 09:00
CRDT- 2004/01/23 05:00
PHST- 2004/01/23 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/01/23 05:00 [entrez]
AID - 10.1093/ndt/gfg583 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2004 Feb;19(2):312-9. doi: 10.1093/ndt/gfg583.