Evidence map›Paper›PMID 23296709›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

Activation of TLR4 is required for the synergistic induction of dual oxidase 2 and dual oxidase A2 by IFN-γ and lipopolysaccharide in human pancreatic cancer cell lines.

Yongzhong Wu, Jiamo Lu, Smitha Antony, Agnes Juhasz, Han Liu, Guojian Jiang, Jennifer L Meitzler, Melinda Hollingshead, Diana C Haines, Donna Butcher and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

47 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
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  7. NOX Family: Regulators of Reactive Oxygen Species Balance in Tumor Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  20. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging".Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020
    Review
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

12 authors at 5 institutions in 1 country.

Yongzhong WuLaboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jiamo Lu
Smitha Antony
Agnes Juhasz
Han Liu
Guojian Jiang
Jennifer L Meitzler
Melinda Hollingshead
Diana C Haines
Donna Butcher
Krishnendu Roy
James H Doroshow
National Institutes of Health · USNational Cancer Institute · USCenter for Cancer Research · USFrederick National Laboratory for Cancer Research · USScience Applications International Corporation (United States) · US

Funding

Roles of NADPH Oxidase 5 and Dual Oxidase 2 in CancerZIABC011076 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES · 2009 to 2016
$4.6M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA BC011076NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Pancreatitis is associated with release of proinflammatory cytokines and reactive oxygen species and plays an important role in the development of pancreatic cancer. We recently demonstrated that dual oxidase (Duox)2, an NADPH oxidase essential for reactive oxygen species-related, gastrointestinal host defense, is regulated by IFN-γ-mediated Stat1 binding to the Duox2 promoter in pancreatic tumor lines. Because LPS enhances the development and invasiveness of pancreatic cancer in vivo following TLR4-related activation of NF-κB, we examined whether LPS, alone or combined with IFN-γ, regulated Duox2. We found that upregulation of TLR4 by IFN-γ in BxPC-3 and CFPAC-1 pancreatic cancer cells was augmented by LPS, resulting in activation of NF-κB, accumulation of NF-κB (p65) in the nucleus, and increased binding of p65 to the Duox2 promoter. TLR4 silencing with small interfering RNAs, as well as two independent NF-κB inhibitors, attenuated LPS- and IFN-γ-mediated Duox2 upregulation in BxPC-3 cells. Induction of Duox2 expression by IFN-γ and LPS may result from IFN-γ-related activation of Stat1 acting in concert with NF-κB-related upregulation of Duox2. Sustained extracellular accumulation of H(2)O(2) generated by exposure to both LPS and IFN-γ was responsible for an ∼50% decrease in BxPC-3 cell proliferation associated with a G(1) cell cycle block, apoptosis, and DNA damage. We also demonstrated upregulation of Duox expression in vivo in pancreatic cancer xenografts and in patients with chronic pancreatitis. These results suggest that inflammatory cytokines can interact to produce a Duox-dependent pro-oxidant milieu that could increase the pathologic potential of pancreatic inflammation and pancreatic cancer cells.

Indexed as

AnimalsCell Line, TumorChronic DiseaseDual OxidasesFemaleHumansInterferon-gammaLipopolysaccharidesMembrane ProteinsMiceMice, NudeNADPH OxidasesNeoplasm TransplantationPancreatic NeoplasmsPancreatitisRandom AllocationDual OxidasesDUOX2 protein, humanDUOXA2 protein, humanInterferon-gammaLipopolysaccharidesMembrane ProteinsNADPH OxidasesReactive Oxygen SpeciesTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID23296709
PMCPMC3563939
OpenAlexW2112610954

What OpenQuestion holds

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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.