Evidence map›Paper›PMID 21303924›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2011

Differential role of Toll-interleukin 1 receptor domain-containing adaptor protein in Toll-like receptor 2-mediated regulation of gene expression of hepatic cytokines and drug-metabolizing enzymes.

Romi Ghose, Tao Guo, Jesus G Vallejo, Adarsh Gandhi

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Role of Toll-like receptor 4 in drug-drug interaction between paclitaxel and irinotecan in vitro.Toxicology in vitro : an international journal published in association with BIBRA · 2017
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. 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

4 authors at 1 institution in 1 country.

Romi GhoseCollege of Pharmacy, Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 1441 Moursund St., Houston, TX 77030, USA. rghose@uh.edu
Tao Guo
Jesus G Vallejo
Adarsh Gandhi
University of Houston · US

Funding

Hepatic drug metabolism in inflammationK01DK076057 · NIDDK · UNIVERSITY OF HOUSTON · PI GHOSE, ROMI · 2006 to 2009
$563k
NIDDK NIH HHS K01 DK076057NIDDK NIH HHS K01-DK076057-02
6 · The paper itself

Abstract

Pharmacological activities of drugs are impaired during inflammation because of reduced expression of hepatic drug-metabolizing enzyme genes (DMEs) and their regulatory nuclear receptors (NRs): pregnane X receptor (PXR), constitutive androstane receptor (CAR), and retinoid X receptor (RXRα). We have shown that a component of Gram-positive bacteria, lipoteichoic acid (LTA) induces proinflammatory cytokines and reduces gene expression of hepatic DMEs and NRs. LTA is a Toll-like receptor 2 (TLR2) ligand, which initiates signaling by recruitment of Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) to the cytoplasmic TIR domain of TLR2. To determine the role of TIRAP in TLR2-mediated regulation of DME genes, TLR2(+/+), TLR2(-/-), TIRAP(+/+), and TIRAP(-/-) mice were given LTA injections. RNA levels of the DMEs (Cyp3a11, Cyp2b10, and sulfoaminotransferase), xenobiotic NRs (PXR and CAR), and nuclear protein levels of the central NR RXRα were reduced ∼ 50 to 60% in LTA-treated TLR2(+/+) but not in TLR2(-/-) mice. Induction of hepatic cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6), c-Jun NH(2)-terminal kinase, and nuclear factor-κΒ was blocked in TLR2(-/-) mice. As expected, expression of hepatic DMEs and NRs was reduced by LTA in TIRAP(+/+) but not in TIRAP(-/-) mice. Of interest, cytokine RNA levels were induced in the livers of both the TIRAP(+/+) and TIRAP(-/-) mice, whereas LTA-mediated induction of serum cytokines was attenuated in TIRAP(-/-) mice. LTA-mediated down-regulation of DME genes was attenuated in hepatocytes from TLR2(-/-) or TIRAP(-/-) mice and in small interfering RNA-treated hepatocytes. Thus, the effect of TLR2 on DME genes in hepatocytes was mediated by TIRAP, whereas TIRAP was not involved in mediating the effects of TLR2 on cytokine expression in the liver.

Indexed as

AnimalsCells, CulturedCytochrome P-450 Enzyme SystemCytokinesDown-RegulationGene ExpressionHepatocytesInactivation, MetabolicLipopolysaccharidesLiverMaleMembrane GlycoproteinsMetabolic Detoxication, Phase IMetabolic Detoxication, Phase IIMiceMice, Inbred C57BLCytochrome P-450 Enzyme SystemCytokinesLipopolysaccharideslipoteichoic acidMembrane GlycoproteinsReceptors, Cytoplasmic and NuclearReceptors, Interleukin-1Teichoic AcidsTIRAP protein, mouseToll-Like Receptor 2

Identifiers

PMID21303924
PMCPMC3082375
OpenAlexW2126880098

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.