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Series GSE71263 Query DataSets for GSE71263
Status Public on May 12, 2016
Title Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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. 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 Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
Overall design Gene expression in BMDMs obtained from wild-type and Keap1-CKO mice. In Keap1-CKO (Keap1 flox/flox::LysM-Cre) BMDMs, Nrf2 transcription factor is activated due to Keap1-deficiency. BMDMs were obtained by a culture of bone marrow cells in the presence of M-CSF for7 days. M1-activated BMDMs were obtained by stimulation with LPS and IFNg for 6 hours, while M2-activated BMDMs were obtained by a stimulation with IL-4 for 6 hours. Two independent BMDM cultures were performed, and each experiment contains samples obtained from one wild-type and one Keap1-CKO mice, respectively.
Contributor(s) Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Moriguchi T, Nakayama K, Yamamoto M
Citation(s) 27211851
Submission date Jul 23, 2015
Last update date Jan 12, 2017
Contact name Eri H Kobayashi
Organization name Tohoku University Graduate School of Medicine
Department Medical Biochemistry
Street address 2-1 Seiryo-machi, Aobaku
City Sendai
State/province Miyagi
ZIP/Postal code 980-8575
Country Japan
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (12)
GSM1831605 BMDMs_WT_replicate1
GSM1831606 BMDMs_WT_replicate2
GSM1831607 BMDMs_Keap1CKO_replicate1
BioProject PRJNA290721

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE71263_RAW.tar 26.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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