Evidence map›Paper›PMID 25957295›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015

Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function.

Thomas E Sussan, Sachin Gajghate, Samit Chatterjee, Pooja Mandke, Sarah McCormick, Kuladeep Sudini, Sarvesh Kumar, Patrick N Breysse, Gregory B Diette, Venkataramana K Sidhaye and 1 more

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

55 citing papers in PubMed, 93 citations in OpenAlex.

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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.

Thomas E SussanDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and tsussan1@jhu.edu.
Sachin GajghateDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Samit ChatterjeeDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Pooja MandkeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Sarah McCormickDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Kuladeep SudiniDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Sarvesh KumarDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Patrick N BreysseDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Gregory B DietteDivision of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Venkataramana K SidhayeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Shyam BiswalDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Oxidative Stress & Inflammation in a Human PM Nasal ChallengeP50ES015903 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI BREYSSE, PATRICK N · 2007 to 2011
$12.1M
Project 3: Dissecting the Diet Asthma Relationship in Mice Models of AsthmaP01ES018176 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 2009 to 2013
$4.2M
Mentoring and Patient Oriented Research in AsthmaK24ES021098 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI DIETTE, GREGORY B · 2012 to 2016
$927k
NIEHS NIH HHS K24 ES021098NIEHS NIH HHS P01-ES-018176NIEHS NIH HHS P50-ES-015903
6 · The paper itself

Abstract

Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAsthmaBronchial HyperreactivityCadherinsChalconesCytokinesCytoprotectionCytoskeletal ProteinsEpithelial CellsInflammationKelch-Like ECH-Associated Protein 1LungMaleMiceMice, Inbred C57BL2-trifluoromethyl-2'-methoxychaloneAdaptor Proteins, Signal TransducingCadherinsChalconesCytokinesCytoskeletal ProteinsKeap1 protein, mouseKelch-Like ECH-Associated Protein 1Nfe2l2 protein, mouseNF-E2-Related Factor 2OvalbuminZonula Occludens-1 Proteinairway hyperresponsivenessinflammationovalbuminoxidative stressTh2

Identifiers

PMID25957295
PMCPMC4491510
OpenAlexW1893923004

What OpenQuestion holds

Textmetadata
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.