Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription

Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. Chromatin immunoprecipitation (ChIP)-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2-binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that…

• JA
  Japan Agency for Medical Research and Development

  Award: CREST
• MO
  Ministry of Education, Culture, Sports, Science and Technology

  Awards: 23116002, 22118002, CREST
• JS
  Japan Society for the Promotion of Science

  Awards: 24249015, 25840001, CREST, 15K08257
• CR
  Core Research for Evolutional Science and Technology