A negative autoregulatory link between Nramp1 function and expression
A negative autoregulatory link between Nramp1 function and expression
Nramp1 (natural resistance-associated macrophage protein) controls resistance to infection by intracellular pathogens in mice. Nramp1 regulates the microenvironment of the invading pathogen by increasing the luminal iron that participates in the Haber-Weiss reaction, producing radicals that attack the pathogen. We have studied the effect of inflammatory stimuli, iron, and sodium nitroprusside on Nramp1 expression in bone marrow macrophages. Investigations show all three up-regulate Nramp1 expression with a parallel increase in immunoreactivity to an amino-terminal antibody and Nramp1 mRNA. Growth rates are reduced in macrophage cell lines expressing Nramp1. This is through a decrease in iron availability, shown by an increase in IRP2 activity and a reciprocal decrease in conventional protein kinase Cbeta-1 expression. We propose that Nramp1 activity may control its own expression via a negative autoregulatory loop that is important for iron homeostasis and maintenance of low cytoplasmic redox active iron levels in the macrophage.
501-507
Baker, S.T.
359e3325-2545-44e5-a64d-8d4a433d8af7
Barton, C.H.
5dfb4e1a-d559-4b58-9036-31de1e6c9ad8
Biggs, T.E.
5ef9af49-c9ba-44ed-b9b1-2aacdc5bee2d
April 2000
Baker, S.T.
359e3325-2545-44e5-a64d-8d4a433d8af7
Barton, C.H.
5dfb4e1a-d559-4b58-9036-31de1e6c9ad8
Biggs, T.E.
5ef9af49-c9ba-44ed-b9b1-2aacdc5bee2d
Baker, S.T., Barton, C.H. and Biggs, T.E.
(2000)
A negative autoregulatory link between Nramp1 function and expression.
Journal of Leukocyte Biology, 67 (4), .
Abstract
Nramp1 (natural resistance-associated macrophage protein) controls resistance to infection by intracellular pathogens in mice. Nramp1 regulates the microenvironment of the invading pathogen by increasing the luminal iron that participates in the Haber-Weiss reaction, producing radicals that attack the pathogen. We have studied the effect of inflammatory stimuli, iron, and sodium nitroprusside on Nramp1 expression in bone marrow macrophages. Investigations show all three up-regulate Nramp1 expression with a parallel increase in immunoreactivity to an amino-terminal antibody and Nramp1 mRNA. Growth rates are reduced in macrophage cell lines expressing Nramp1. This is through a decrease in iron availability, shown by an increase in IRP2 activity and a reciprocal decrease in conventional protein kinase Cbeta-1 expression. We propose that Nramp1 activity may control its own expression via a negative autoregulatory loop that is important for iron homeostasis and maintenance of low cytoplasmic redox active iron levels in the macrophage.
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Published date: April 2000
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Local EPrints ID: 56712
URI: http://eprints.soton.ac.uk/id/eprint/56712
ISSN: 0741-5400
PURE UUID: 105e4efe-cd91-4d6b-8cab-2b0141016a92
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Date deposited: 21 Aug 2008
Last modified: 08 Jan 2022 10:05
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Author:
S.T. Baker
Author:
T.E. Biggs
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