PMID- 15284299
OWN - NLM
STAT- MEDLINE
DCOM- 20040920
LR  - 20220317
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 15
IP  - 8
DP  - 2004 Aug
TI  - Interactions between angiotensin II and NF-kappaB-dependent pathways in 
      modulating macrophage infiltration in experimental diabetic nephropathy.
PG  - 2139-51
AB  - NF-kappaB-dependent pathways play an important role in macrophage infiltration 
      and kidney injury. NF-kappaB is regulated by angiotensin II (AII). However, the 
      role of this pathway in diabetic nephropathy has not been clearly delineated. 
      First, the activation of NF-kappaB, monocyte chemoattractant protein-1 (MCP-1), 
      and macrophage infiltration in the diabetic kidney were explored, in a temporal 
      manner. The active subunit of NF-kappaB, p65, was elevated in the diabetic 
      animals in association with increased MCP-1 gene expression and macrophage 
      infiltration. Second, the effects of treatment for 4 wk with the AII type 1 
      receptor antagonist valsartan, the AII type 2 receptor antagonist PD123319, or 
      pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB and on these parameters 
      were assessed. These treatments were associated with a reduction in p65 
      activation, MCP-1 gene expression, and macrophage infiltration. These findings 
      demonstrate a role for activation of NF-kappaB, in particular the p65 subunit, in 
      the pathogenesis of early renal macrophage infiltration in experimental diabetes. 
      In the context of the known proinflammatory effects of AII, it is postulated that 
      the renoprotection conferred by angiotensin II receptor antagonism is at least 
      partly related to the inhibition of NF-kappaB-dependent pathways.
FAU - Lee, Fiona T H
AU  - Lee FT
AD  - Danielle Alberti Memorial Centre for Diabetic Complications, Vascular Division, 
      Baker Medical Research Institute, Melbourne 8008, Australia.
FAU - Cao, Zemin
AU  - Cao Z
FAU - Long, David M
AU  - Long DM
FAU - Panagiotopoulos, Sianna
AU  - Panagiotopoulos S
FAU - Jerums, George
AU  - Jerums G
FAU - Cooper, Mark E
AU  - Cooper ME
FAU - Forbes, Josephine M
AU  - Forbes JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Angiotensin II Type 2 Receptor Blockers)
RN  - 0 (Antioxidants)
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Pyrrolidines)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Thiocarbamates)
RN  - 0 (Transcription Factor RelA)
RN  - 11128-99-7 (Angiotensin II)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Angiotensin II Type 1 Receptor Blockers
MH  - Angiotensin II Type 2 Receptor Blockers
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Biomarkers
MH  - Chemokine CCL2/genetics
MH  - Diabetic Nephropathies/metabolism/*pathology
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression
MH  - I-kappa B Proteins/metabolism
MH  - Macrophages/*pathology
MH  - Male
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Receptor, Angiotensin, Type 2/metabolism
MH  - Thiocarbamates/pharmacology
MH  - Transcription Factor RelA
EDAT- 2004/07/31 05:00
MHDA- 2004/09/21 05:00
CRDT- 2004/07/31 05:00
PHST- 2004/07/31 05:00 [pubmed]
PHST- 2004/09/21 05:00 [medline]
PHST- 2004/07/31 05:00 [entrez]
AID - 15/8/2139 [pii]
AID - 10.1097/01.ASN.0000135055.61833.A8 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2004 Aug;15(8):2139-51. doi: 
      10.1097/01.ASN.0000135055.61833.A8.