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Title: Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells

Abstract

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-1{alpha} (HIF-1{alpha}) in HPTECs. Desferrioxamine mimicked hypoxia in the reduction of MCP-1 expression. However, overexpression of a dominant negative form of HIF-1{alpha} 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.

Authors:
 [1];  [1];  [2];  [1];  [1]
  1. Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)
  2. Department of Anesthesia, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka (Japan)
Publication Date:
OSTI Identifier:
20711006
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 335; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2005.07.175; PII: S0006-291X(05)01673-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTINOMYCIN; ANOXIA; GENE REGULATION; IRON; KIDNEYS; MACROPHAGES; MONOCYTES; PROTEINS; TIME DEPENDENCE; TRANSCRIPTION

Citation Formats

Xuan, Li, Kimura, Hideki, Hirota, Kiichi, Department of Anesthesia, School of Medicine, Kyoto University, Kyoto, Sugimoto, Hidehiro, and Yoshida, Haruyoshi. Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.07.175.
Xuan, Li, Kimura, Hideki, Hirota, Kiichi, Department of Anesthesia, School of Medicine, Kyoto University, Kyoto, Sugimoto, Hidehiro, & Yoshida, Haruyoshi. Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells. United States. https://doi.org/10.1016/j.bbrc.2005.07.175
Xuan, Li, Kimura, Hideki, Hirota, Kiichi, Department of Anesthesia, School of Medicine, Kyoto University, Kyoto, Sugimoto, Hidehiro, and Yoshida, Haruyoshi. 2005. "Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells". United States. https://doi.org/10.1016/j.bbrc.2005.07.175.
@article{osti_20711006,
title = {Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells},
author = {Xuan, Li and Kimura, Hideki and Hirota, Kiichi and Department of Anesthesia, School of Medicine, Kyoto University, Kyoto and Sugimoto, Hidehiro and Yoshida, Haruyoshi},
abstractNote = {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-1{alpha} (HIF-1{alpha}) in HPTECs. Desferrioxamine mimicked hypoxia in the reduction of MCP-1 expression. However, overexpression of a dominant negative form of HIF-1{alpha} 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.},
doi = {10.1016/j.bbrc.2005.07.175},
url = {https://www.osti.gov/biblio/20711006}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 335,
place = {United States},
year = {Fri Oct 07 00:00:00 EDT 2005},
month = {Fri Oct 07 00:00:00 EDT 2005}
}