PMID- 10331420
OWN - NLM
STAT- MEDLINE
DCOM- 19990527
LR  - 20220331
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 5
DP  - 1999 May
TI  - Vascular endothelial growth factor activates nuclear factor-kappaB and induces 
      monocyte chemoattractant protein-1 in bovine retinal endothelial cells.
PG  - 1131-7
AB  - Vascular endothelial growth factor (VEGF) has been suggested to play a role in 
      the pathogenesis of diabetic vascular complications. In the present study, we 
      investigated whether expression of monocyte chemoattractant protein-1 (MCP-1), a 
      chemokine that has been proposed to recruit leukocytes to sites of inflammation, 
      neovascularization, and vascular injury, can be modulated by VEGF in bovine 
      retinal microvascular endothelial cells (BRECs). VEGF induced expression of MCP-1 
      mRNA in BRECs in a concentration- and time-dependent manner. Secretion of MCP-1 
      into the culture medium of BRECs treated with VEGF for 24 h was increased by 
      2.2-fold compared with the control. Inhibitors of transcription factor NF-kappaB, 
      N-alpha-tosyl-L-lysine chloromethylketone (TLCK) and N-acetylcysteine (NAC), as 
      well as an inhibitor of the extracellular signal-regulated kinase (ERK) pathway, 
      PD 98059, attenuated VEGF-induced expression of MCP-1 mRNA. Using electrophoretic 
      gel mobility shift assay, we observed that VEGF stimulated binding activity of 
      NF-kappaB. VEGF-induced NF-kappaB activation was inhibited by TLCK and NAC, but 
      not by PD 98059. Binding activity of transcription factor AP-1, which is 
      suggested to regulate induction of the MCP-1 gene together with NF-kappaB, was 
      also stimulated by VEGF. PD 98059 inhibited the VEGF-induced activation of AP-1. 
      These results indicate that VEGF induces MCP-1 expression in BRECs most likely by 
      activating NF-kappaB and AP-1 via ERK-independent and -dependent pathways. 
      Activation of NF-kappaB and induction of MCP-1 by VEGF in microvascular 
      endothelial cells may contribute to the development of diabetic vascular 
      complications.
FAU - Marumo, T
AU  - Marumo T
AD  - Institut fur Kardiovaskulare Physiologie, Klinikum der Johann Wolfgang Goethe 
      Universitat, Frankfurt am Main, Germany. r.busse@em.uni-frankfurt.de
FAU - Schini-Kerth, V B
AU  - Schini-Kerth VB
FAU - Busse, R
AU  - Busse R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 2104-86-1 (Tosyllysine Chloromethyl Ketone)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Cattle
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Endothelial Growth Factors/*pharmacology
MH  - Endothelium, Vascular/*metabolism
MH  - Gene Expression
MH  - Kinetics
MH  - Lymphokines/*pharmacology
MH  - Microcirculation/metabolism
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Retinal Vessels/*metabolism
MH  - Tosyllysine Chloromethyl Ketone/pharmacology
MH  - Transcription Factor AP-1/metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.2337/diabetes.48.5.1131 [doi]
PST - ppublish
SO  - Diabetes. 1999 May;48(5):1131-7. doi: 10.2337/diabetes.48.5.1131.