Evidence map›Paper›PMID 18423053›Full record

ArticleBMC molecular biology2008

DNA demethylation-dependent enhancement of toll-like receptor-2 gene expression in cystic fibrosis epithelial cells involves SP1-activated transcription.

Takashi Furuta, Tsuyoshi Shuto, Shogo Shimasaki, Yuko Ohira, Mary Ann Suico, Dieter C Gruenert, Hirofumi Kai

Open access · hybridAbstract read
In one paragraph

Article in BMC molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.8field-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

19 citing papers in PubMed, 53 citations in OpenAlex.

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  16. DNA Methylation Profiles of Protease Nexin 1 (SERPINE2) Gene in Human Cell Lines.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2011
    Article
  17. Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3.American journal of physiology. Lung cellular and molecular physiology · 2010
    Article
  18. TLR-4-mediated innate immunity is reduced in cystic fibrosis airway cells.American journal of respiratory cell and molecular biology · 2010
    Article
  19. TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2009
    Article
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

7 authors at 2 institutions in 2 countries.

Takashi FurutaDepartment of Molecular Medicine, Graduate School of Pharmaceutical Science, Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Kumamoto 862-0973, Japan. furutakashi@molmed730.com
Tsuyoshi Shuto
Shogo Shimasaki
Yuko Ohira
Mary Ann Suico
Dieter C Gruenert
Hirofumi Kai
Kumamoto University · JPCalifornia Pacific Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe clinical course of cystic fibrosis (CF) is characterized by recurrent pulmonary infections and chronic inflammation. We have recently shown that decreased methylation of the toll-like receptor-2 (TLR2) promoter leads to an apparent CF-related up-regulation of TLR2. This up-regulation could be responsible, in part, for the CF-associated enhanced proinflammatory responses to various bacterial products in epithelial cells. However, the molecular mechanisms underlying DNA hypomethylation-dependent enhancement of TLR2 expression in CF cells remain unknown.

resultsThe present study indicates that there is a specific CpG region (CpG#18-20), adjacent to the SP1 binding site that is significantly hypomethylated in several CF epithelial cell lines. These CpGs encompass a minimal promoter region required for basal TLR2 expression, and suggests that CpG#18-20 methylation regulates TLR2 expression in epithelial cells. Furthermore, reporter gene analysis indicated that the SP1 binding site is involved in the methylation-dependent regulation of the TLR2 promoter. Inhibition of SP1 with mithramycin A decreased TLR2 expression in both CF and 5-azacytidine-treated non-CF epithelial cells. Moreover, even though SP1 binding was not affected by CpG methylation, SP1-dependent transcription was abolished by CpG methylation.

conclusionThis report implicates SP1 as a critical component of DNA demethylation-dependent up-regulation of TLR2 expression in CF epithelial cells.

Indexed as

DNA MethylationGene Expression RegulationTranscription, GeneticBinding SitesCell LineCpG IslandsCystic FibrosisEpithelial CellsHumansModels, BiologicalPromoter Regions, GeneticProtein BindingSp1 Transcription FactorToll-Like Receptor 2Sp1 Transcription FactorToll-Like Receptor 2

Identifiers

PMID18423053
PMCPMC2387165
OpenAlexW2007811208

What OpenQuestion holds

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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.