Evidence map›Paper›PMID 27211851›Full record

ArticleNature communications2016

Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription.

Eri H Kobayashi, Takafumi Suzuki, Ryo Funayama, Takeshi Nagashima, Makiko Hayashi, Hiroki Sekine, Nobuyuki Tanaka, Takashi Moriguchi, Hozumi Motohashi, Keiko Nakayama and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 983 papers.

0numbers the graph read from it
0cells of the map it votes in
983citing papers in PubMed
51.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

983 citing papers in PubMed, 1,763 citations in OpenAlex.

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  14. Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
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  17. Genetic and pharmacologic modulations elucidate NRF2 protective role in acute pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  18. Article
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923 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Eri H KobayashiDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Takafumi SuzukiDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Ryo FunayamaDivision of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Takeshi NagashimaDivision of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Makiko HayashiDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Hiroki SekineDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Nobuyuki TanakaDivision of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
Takashi MoriguchiDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Hozumi MotohashiDepartment of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.ORCID http://orcid.org/0000-0002-7261-1033
Keiko NakayamaDivision of Cell Proliferation, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Masayuki YamamotoDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Tohoku University · JPMiyagi Prefectural Hospital Organization · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 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.

Indexed as

Gene Expression RegulationAnimalsCytokinesInflammationMacrophagesMice, Inbred C57BLMice, Inbred ICRMice, KnockoutNF-E2-Related Factor 2Oxidative StressRNA Polymerase IICytokinesNfe2l2 protein, mouseNF-E2-Related Factor 2RNA Polymerase II

Identifiers

PMID27211851
PMCPMC4879264
OpenAlexW2400239628

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.