Multiorgan Autoimmune Inflammation, Enhanced Lymphoproliferation, and Impaired Homeostasis of Reactive Oxygen Species in Mice Lacking the Antioxidant-Activated Transcription Factor Nrf2

Details

• Personal Author:
  Battelli L ; Hubbs, Ann F. ; Ma Q
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Blood Genetics Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Antioxidation Autoimmunity Blood-vessels Diseases Genes In-vivo-studies In-vivo-study Laboratory-animals
• ISSN:
  0002-9440
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  168
• Issue:
  6
• NIOSHTIC Number:
  nn:20030384
• Citation:
  Am J Pathol 2006 Jun; 168(6):1960-1974
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2006
• Peer Reviewed:
  True
• Source Full Name:
  The American Journal of Pathology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1e2153dcb276ad5e8957b65a27909d550ad0f59f880ae6d2fb52230933fadaa08145d3e5cfb1798e039fc19b325d441490db71e8637416b043de4df5116d2f5a
• Download URL:
  https://stacks.cdc.gov/view/cdc/191033/cdc_191033_DS1.pdf
• File Type:
  [PDF - 2.20 MB ]