PMID- 10844599
OWN - NLM
STAT- MEDLINE
DCOM- 20000824
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 57
IP  - 6
DP  - 2000 Jun
TI  - Angiotensin III increases MCP-1 and activates NF-kappaB and AP-1 in cultured 
      mesangial and mononuclear cells.
PG  - 2285-98
AB  - BACKGROUND: Monocyte infiltration is a common feature of renal diseases. 
      Angiotensin II (Ang II) participates in inflammatory cell infiltration in the 
      kidney. However, the influence of other peptides of the renin-angiotensin system, 
      such as the N-terminal Ang II degradation product Ang III, has not been 
      addressed. METHODS: In cultured renal and mononuclear cells, we investigated 
      whether Ang III is involved in monocyte recruitment through the regulation of the 
      chemokine, monocyte chemoattractant protein-1 (MCP-1; Northern blot, Western 
      blot, immunofluorescence, and chemotaxis), and the activation of transcription 
      factors, nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1; 
      electrophoretic mobility shift assay). RESULTS: In cultured rat mesangial and 
      mononuclear cells, Ang III increased MCP-1 gene expression and protein levels. 
      Supernatants from Ang III-treated mesangial cells showed increased 
      chemoattractant activity for monocytes, which was partially inhibited by the 
      addition of anti-MCP-1 antibody. Ang III elicited a rapid NF-kappaB activation 
      (8-fold, after 30 min), showing a kinetics and intensity similar to that observed 
      with Ang II and tumor necrosis factor-alpha. The maximal NF-kappaB activation was 
      correlated with nuclear translocation of p50 and p65 subunits and disappearance 
      of cytosolic IkappaB. Ang III also activated AP-1 (5-fold, after 18 h), while 
      SP-1 was unchanged. Two NF-kappaB inhibitors abolished the Ang III-induced MCP-1 
      mRNA expression, suggesting that overexpression of this chemokine is mediated, at 
      least in part, by NF-kappaB activation. CONCLUSIONS: Ang III activates the 
      transcription factors NF-kappaB and AP-1 and increases the expression of related 
      genes, such as MCP-1. Our study describes a novel and potent proinflammatory 
      action of this Ang degradation product, expanding the present view of the 
      renin-angiotensin system.
FAU - Ruiz-Ortega, M
AU  - Ruiz-Ortega M
AD  - Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.
FAU - Lorenzo, O
AU  - Lorenzo O
FAU - Egido, J
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 12687-51-3 (Angiotensin III)
SB  - IM
MH  - Angiotensin III/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Glomerular Mesangium/cytology/drug effects/*metabolism
MH  - Monocytes/drug effects/*metabolism
MH  - NF-kappa B/*physiology
MH  - Protein Isoforms/genetics/physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Transcription Factor AP-1/*physiology
EDAT- 2000/06/09 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/06/09 09:00
PHST- 2000/06/09 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/06/09 09:00 [entrez]
AID - S0085-2538(15)46989-3 [pii]
AID - 10.1046/j.1523-1755.2000.00089.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Jun;57(6):2285-98. doi: 10.1046/j.1523-1755.2000.00089.x.