TY - JOUR
KW - Animals
KW - Autoimmune Diseases
KW - Cation Transport Proteins
KW - Cell Line
KW - COS Cells
KW - DNA
KW - DNA-Binding Proteins
KW - Drug Synergism
KW - Gene Expression
KW - Genetic Vectors
KW - HL-60 Cells
KW - Humans
KW - Immunity, Innate
KW - Interferon Regulatory Factors
KW - Interferon-gamma
KW - Kruppel-Like Transcription Factors
KW - Lipopolysaccharides
KW - Macrophages
KW - Mice
KW - Mice, Knockout
KW - NIH 3T3 Cells
KW - Proto-Oncogene Proteins
KW - Recombinant Fusion Proteins
KW - Repressor Proteins
KW - Saccharomyces cerevisiae
KW - Trans-Activators
KW - Transcription Factors
KW - Transfection
KW - Two-Hybrid System Techniques
AU - Alter-Koltunoff M
AU - Ehrlich S
AU - Dror N
AU - Azriel A
AU - Eilers M
AU - Hauser H
AU - Bowen H
AU - Barton H
AU - Tamura T
AU - Ozato K
AU - Levi B
AB - <p>Natural resistance-associated macrophage protein 1 (Nramp1) is a proton/divalent cation antiporter exclusively expressed in monocyte/macrophage cells with a unique role in innate resistance to intraphagosomal pathogens. In humans, it is linked to several infectious diseases, including leprosy, pulmonary tuberculosis, visceral leishmaniasis, meningococcal meningitis, and human immunodeficiency virus as well as to autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Here we demonstrate that the restricted expression of Nramp1 is mediated by the macrophage-specific transcription factor IRF-8. This factor exerts its activity via protein-protein interaction, which facilitates its binding to target DNA. Using yeast two-hybrid screen we identified Myc Interacting Zinc finger protein 1 (Miz-1) as new interacting partner. This interaction is restricted to immune cells and takes place on the promoter Nramp1 in association with PU.1, a transcription factor essential for myelopoiesis. Consistent with these data, IRF-8 knockout mice are sensitive to a repertoire of intracellular pathogens. Accordingly, IRF-8-/- mice express low levels of Nramp1 that can not be induced any further. Thus, our results explain in molecular terms the role of IRF-8 in conferring innate resistance to intracellular pathogens and point to its possible involvement in autoimmune diseases.</p>
BT - The Journal of biological chemistry
C1 - http://www.ncbi.nlm.nih.gov/pubmed/12904288?dopt=Abstract
DA - 2003 Nov 07
DO - 10.1074/jbc.M307954200
IS - 45
J2 - J. Biol. Chem.
LA - eng
N2 - <p>Natural resistance-associated macrophage protein 1 (Nramp1) is a proton/divalent cation antiporter exclusively expressed in monocyte/macrophage cells with a unique role in innate resistance to intraphagosomal pathogens. In humans, it is linked to several infectious diseases, including leprosy, pulmonary tuberculosis, visceral leishmaniasis, meningococcal meningitis, and human immunodeficiency virus as well as to autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Here we demonstrate that the restricted expression of Nramp1 is mediated by the macrophage-specific transcription factor IRF-8. This factor exerts its activity via protein-protein interaction, which facilitates its binding to target DNA. Using yeast two-hybrid screen we identified Myc Interacting Zinc finger protein 1 (Miz-1) as new interacting partner. This interaction is restricted to immune cells and takes place on the promoter Nramp1 in association with PU.1, a transcription factor essential for myelopoiesis. Consistent with these data, IRF-8 knockout mice are sensitive to a repertoire of intracellular pathogens. Accordingly, IRF-8-/- mice express low levels of Nramp1 that can not be induced any further. Thus, our results explain in molecular terms the role of IRF-8 in conferring innate resistance to intracellular pathogens and point to its possible involvement in autoimmune diseases.</p>
PY - 2003
SP - 44025
EP - 32
T2 - The Journal of biological chemistry
TI - Nramp1-mediated innate resistance to intraphagosomal pathogens is regulated by IRF-8, PU.1, and Miz-1.
VL - 278
SN - 0021-9258
ER -