PMID- 16105652
OWN - NLM
STAT- MEDLINE
DCOM- 20051114
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 335
IP  - 4
DP  - 2005 Oct 7
TI  - Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte 
      chemoattractant protein-1 in human proximal renal tubular cells.
PG  - 1026-34
AB  - Chronic hypoxia has been reported to be associated with macrophage infiltration 
      in progressive forms of kidney disease. Here, we investigated the regulatory 
      effects of hypoxia on constitutive and TNF-alpha-stimulated expression of 
      monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal renal 
      tubular cells (HPTECs). Hypoxia reduced constitutive MCP-1 expression at the mRNA 
      and protein levels in a time-dependent fashion for up to 48 h. Hypoxia also 
      inhibited MCP-1 up-regulation by TNF-alpha. Treatment with actinomycin D showed 
      that hypoxic down-regulation of MCP-1 expression resulted mainly from a decrease 
      in the transcription but not the mRNA stability. Immunoblot and 
      immunofluorescence analyses revealed that treatment with hypoxia or an iron 
      chelator, desferrioxamine, induced nuclear accumulation of hypoxia-inducible 
      factor-1alpha (HIF-1alpha) in HPTECs. Desferrioxamine mimicked hypoxia in the 
      reduction of MCP-1 expression. However, overexpression of a dominant negative 
      form of HIF-1alpha did not abolish the hypoxia-induced reduction of MCP-1 
      expression in HPTECs. These results suggest that hypoxia is an important negative 
      regulator of monocyte chemotaxis to the renal inflamed interstitium, by reducing 
      MCP-1 expression partly via hypoxia-activated signals other than the HIF-1 
      pathway.
FAU - Li, Xuan
AU  - Li X
AD  - Division of Nephrology, Department of General Medicine, School of Medicine, 
      Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
FAU - Kimura, Hideki
AU  - Kimura H
FAU - Hirota, Kiichi
AU  - Hirota K
FAU - Sugimoto, Hidehiro
AU  - Sugimoto H
FAU - Yoshida, Haruyoshi
AU  - Yoshida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Cell Hypoxia/drug effects/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Kidney Tubules, Proximal/drug effects/*metabolism
MH  - Oxygen/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2005/08/18 09:00
MHDA- 2005/11/15 09:00
CRDT- 2005/08/18 09:00
PHST- 2005/07/28 00:00 [received]
PHST- 2005/07/30 00:00 [accepted]
PHST- 2005/08/18 09:00 [pubmed]
PHST- 2005/11/15 09:00 [medline]
PHST- 2005/08/18 09:00 [entrez]
AID - S0006-291X(05)01673-6 [pii]
AID - 10.1016/j.bbrc.2005.07.175 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2005 Oct 7;335(4):1026-34. doi: 
      10.1016/j.bbrc.2005.07.175.