PMID- 16968890
OWN - NLM
STAT- MEDLINE
DCOM- 20070327
LR  - 20171116
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 292
IP  - 2
DP  - 2007 Feb
TI  - Renal upregulation of HO-1 reduces albumin-driven MCP-1 production: implications 
      for chronic kidney disease.
PG  - F837-44
AB  - Proteinuria contributes to chronic kidney disease by stimulating renal tubular 
      epithelial cells to produce cytokines such as monocyte chemoattractant protein-1 
      (MCP-1). The present study determined whether cellular overexpression of heme 
      oxygenase-1 (HO-1) can influence albumin-stimulated MCP-1 production. In response 
      to bovine serum albumin, NRK-52E cells constitutively overexpressing HO-1 (HO-1 
      OE cells) exhibit less induction of MCP-1 mRNA and less production of MCP-1 
      protein compared with similarly treated, control NRK-52E cells (CON cells). In 
      wild-type NRK-52E cells, and under these conditions, we demonstrate that the 
      induction of MCP-1 is critically dependent on intact NF-kappaB binding sites in 
      the MCP-1 promoter. In response to albumin, CON cells exhibit activation of 
      NF-kappaB, and this is reduced in HO-1 OE cells. Albumin also activates ERK1/2 
      and increases ERK activity, both of which are exaggerated in HO-1 OE cells. 
      Studies with an inhibitor of MAPK/ERK kinase (U0126) demonstrate that the 
      inhibitory effects of U0126 on MCP-1 production are attenuated in HO-1 OE cells. 
      We conclude that HO-1 overexpression in the proximal tubule reduces MCP-1 
      production in response to albumin, and this occurs, at least in part, by 
      inhibiting an ERK-dependent, NF-kappaB-dependent pathway at a site that is distal 
      to the activation of ERK. These findings suggest that the induction of HO-1 in 
      the proximal tubule, as occurs in chronic kidney disease, may be a countervailing 
      response that reduces albumin-stimulated production of cytokines such as MCP-1.
FAU - Murali, Narayana S
AU  - Murali NS
AD  - Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
FAU - Ackerman, Allan W
AU  - Ackerman AW
FAU - Croatt, Anthony J
AU  - Croatt AJ
FAU - Cheng, Jingfei
AU  - Cheng J
FAU - Grande, Joseph P
AU  - Grande JP
FAU - Sutor, Shari L
AU  - Sutor SL
FAU - Bram, Richard J
AU  - Bram RJ
FAU - Bren, Gary D
AU  - Bren GD
FAU - Badley, Andrew D
AU  - Badley AD
FAU - Alam, Jawed
AU  - Alam J
FAU - Nath, Karl A
AU  - Nath KA
LA  - eng
GR  - AI40384/AI/NIAID NIH HHS/United States
GR  - AI62261/AI/NIAID NIH HHS/United States
GR  - DK16105/DK/NIDDK NIH HHS/United States
GR  - DK47060/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060912
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Butadienes)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (U 0126)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis
MH  - Extracellular Signal-Regulated MAP Kinases/biosynthesis
MH  - Heme Oxygenase-1/*biosynthesis
MH  - Kidney/*enzymology
MH  - Kidney Failure, Chronic/*physiopathology
MH  - Kidney Tubules, Proximal/drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitriles/pharmacology
MH  - Rats
MH  - Serum Albumin, Bovine/*pharmacology
MH  - Up-Regulation
EDAT- 2006/09/14 09:00
MHDA- 2007/03/28 09:00
CRDT- 2006/09/14 09:00
PHST- 2006/09/14 09:00 [pubmed]
PHST- 2007/03/28 09:00 [medline]
PHST- 2006/09/14 09:00 [entrez]
AID - 00254.2006 [pii]
AID - 10.1152/ajprenal.00254.2006 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2007 Feb;292(2):F837-44. doi: 
      10.1152/ajprenal.00254.2006. Epub 2006 Sep 12.