PMID- 10361858
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20220409
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 10
IP  - 6
DP  - 1999 Jun
TI  - Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear 
      factor kappaB in proximal tubule cells.
PG  - 1204-13
AB  - The transcription and translation of monocyte chemoattractant protein-1 (MCP-1), 
      a CC chemokine, are increased in proximal tubule epithelial cells (PTC) 
      stimulated with pathophysiologically relevant concentrations of albumin. The 
      purpose of this study was to investigate whether nuclear factor kappaB 
      (NFkappaB)/Rel proteins play a role in albumin-induced MCP-1 transcription. 
      Confluent monolayers of rat PTC in primary culture were stimulated with 
      delipidated bovine serum albumin. NFkappaB, the NFkappaB inhibitory protein 
      (IkappaB), and MCP-1 transcription were assessed using electrophoretic mobility 
      shift assays, Western immunoblotting, semiquantitative reverse transcription-PCR, 
      and ribonuclease protection assays. Activation of NFkappaB by delipidated bovine 
      serum albumin (15 mg/ml) was detectable within 2 h, maximal after 8 h, and 
      maintained for at least 16 h of continuous exposure. Supershift analysis showed 
      that the activated proteins were composed of p50/p50, p50/p65, and p50/c-Rel 
      dimers. dimers. Cytoplasmic IkappaBalpha levels were decreased 30 min after 
      stimulation and returned to unstimulated levels by 4 to 8 h. IkappaBbeta levels 
      were decreased at 2 h and there was no recovery until 8 h. Inhibition of NFkappaB 
      with pharmacologic agents (N-tosyl-phenylalanine chloromethyl ketone and 
      dexamethasone) and an antisense oligonucleotide to the rat p65 subunit of 
      NFkappaB significantly reduced MCP-1 transcription. The 3.6-kb 5' flanking region 
      of the rat MCP-1 gene was cloned and sequenced, and two putative kappaB binding 
      sites were identified within the enhancer region. Therefore, albumin increased 
      NFkappaB and reduced IkappaB levels in PTC, and MCP-1 expression was dependent on 
      NFkappaB activation. It is concluded that the activation of NFkappaB/Rel proteins 
      modulates chemokine production in PTC in response to albumin and is likely to 
      have an important role in the mediation of tubulointerstitial injury in 
      proteinuric renal disease.
FAU - Wang, Y
AU  - Wang Y
AD  - Department of Renal Medicine, The University of Sydney at Westmead Hospital, NSW, 
      Australia.
FAU - Rangan, G K
AU  - Rangan GK
FAU - Tay, Y C
AU  - Tay YC
FAU - Wang, Y
AU  - Wang Y
FAU - Harris, D C
AU  - Harris DC
LA  - eng
PT  - Comparative Study
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 (Albumins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotides)
SB  - IM
MH  - Albumins/*metabolism/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cattle
MH  - Cells, Cultured/metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression Regulation
MH  - Kidney Tubules, Proximal/cytology/*metabolism
MH  - Male
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Oligonucleotides/metabolism/pharmacology
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Rats, Wistar
MH  - Reference Values
MH  - Sensitivity and Specificity
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1681/ASN.V1061204 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1999 Jun;10(6):1204-13. doi: 10.1681/ASN.V1061204.