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Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2.

Authors
Ma-Q; Battelli-L; Hubbs-AF
Source
Am J Pathol 2006 Jun; 168(6):1960-1974
NIOSHTIC No.
20030384
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant-activated cap "n" collar basic leucine zipper transcription factor. To assess the function of Nrf2 in the antioxidant response, we examined mice with targeted disruption of the Nrf2 gene. Nrf2-null mice developed complex disease manifestations, with a majority exhibiting a lupus-like autoimmune syndrome characterized by multiorgan inflammatory lesions with a marked female predominance, appearance of anti-double-stranded DNA antibodies in young adulthood, intravascular deposition of immunoglobulin complexes in blood vessels, and premature death due to rapidly progressing membranoproliferative glomerular nephritis. Mechanistic analyses revealed that the null mice showed enhanced proliferative response of CD4+ T cells, altered ratios of CD4+ and CD8+ cells, and increased oxidative lesions in tissues. Analyses of antioxidant-induced gene expression showed that the knockout mice were devoid of the basal and inducible expression of certain phase 2 detoxification enzymes and antioxidant genes in hepatic and lymphoid cells in vivo. Our findings suggest that Nrf2 mediates important antioxidant functions involved in the control of peripheral lymphocyte homeostasis and autoimmune surveillance.
Keywords
Laboratory-animals; Animals; Animal-studies; Antioxidants; Antioxidation; Genes; Blood-vessels; Diseases; Autoimmunity; In-vivo-studies; In-vivo-study
CODEN
AJPAA4
Publication Date
20060601
Document Type
Journal Article
Email Address
qam1@cdc.gov
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
6
ISSN
0002-9440
NIOSH Division
HELD
Source Name
American Journal of Pathology
State
WV
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