Genome wide analysis of TNF-inducible genes reveals that antioxidant enzymes are induced by TNF and responsible for elimination of ROS

Mol Immunol. 2004 Jul;41(5):547-51. doi: 10.1016/j.molimm.2004.03.030.


We recently showed that TNF induces accumulation of reactive oxygen species (ROS) that mediates necrosis in murine embryonic fibroblasts (MEFs) derived from TRAF2- and TRAF5-double deficient (DKO) mice. To elucidate the defects that subsequently cause accumulation of ROS in DKO MEFs, we compared gene expression profiles of wild-type and DKO MEFs before and after TNF stimulation using cDNA microarrays. Interestingly, many antioxidant enzymes are induced by TNF in wild-type MEFs, induction of these genes is impaired in DKO MEFs. Taken that TNF induces accumulation of ROS in DKO, but not wild-type MEFs, upregulation of antioxidant enzyme(s) might play a crucial role in elimination of ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants
  • Enzymes / genetics*
  • Enzymes / physiology
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Genomics
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Reactive Oxygen Species / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Antioxidants
  • Enzymes
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha