Evidence map›Paper›PMID 11815388›Full record

ArticleBritish journal of pharmacology2002

Redox/ROS regulation of lipopolysaccharide-induced mitogen-activated protein kinase (MAPK) activation and MAPK-mediated TNF-alpha biosynthesis.

J J Haddad, S C Land

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
4.2field-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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Cannabigerol ExertsJournal of microbiology and biotechnology · 2025
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  6. Oxidized Low-Density Lipoprotein and Its Role in Immunometabolism.International journal of molecular sciences · 2024
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. New Insights into the Role of Glutathione in the Mechanism of Fever.International journal of molecular sciences · 2020
    Review
  20. 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

2 authors at 1 institution in 1 country.

J J HaddadOxygen Signalling Group, Centre for Research into Human Development, Tayside Institute of Child Health, Faculty of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY. haddadj@anesthesia.ucsf.edu
S C Land
Ninewells Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Redox and ROS regulation of MAPK-mediated TNF-alpha biosynthesis is not well characterized. It was hypothesized that the involvement of the MAPK pathway in regulating LPS-mediated TNF-alpha secretion is redox-dependent, NF-kappaB-sensitive and attenuated by N-acetyl-L-cysteine (NAC) and other antioxidants. In alveolar epithelial cells, LPS induced a time- and dose-dependent phosphorylation of MAPK(p38). This was associated with the activation of MAPK-activated protein kinase, which phosphorylated the small heat-shock protein, Hsp27. MAPK(p38) inhibition (SB-203580) abrogated LPS-induced TNF-alpha production. MAPK(ERK) blockade (PD-98059) attenuated TNF-alpha secretion, an effect synergistically amplified in the presence of SB-203580. Regulation of NF-kappaB by selective inhibitors revealed that this pathway is partially involved in regulating LPS-mediated TNF-alpha secretion. Whereas the proteasome inhibitor, MG-132, had no effect on LPS-mediated TNF-alpha production, CAPE, sulfasalazine and SN-50, a cell-permeant NF-kappaB inhibitor, attenuated but did not abrogate TNF-alpha biosynthesis. LPS up-regulated ROS, an effect abrogated by 4'-hydroxy-3'-methoxy-acetophenone and NAC, which reduced TNF-alpha secretion, induced the accumulation of GSH, reduced the concentration of GSSG, and blockaded the phosphorylation/activation of MAPK(p38) pathway. ROS induced MAPK(p38) phosphorylation and selective antioxidants, including the permeant GSH precursor, gamma-GCE, reduced ROS-dependent MAPK(p38) phosphorylation. These results indicate that the MAPK pathway and MAPK-mediated regulation of TNF-alpha production is redox-dependent, GSH-mediated and requires, at least in part, a NF-kappaB/ROS-sensitive mechanism.

Indexed as

AcetylcysteineAnimalsCulture TechniquesDose-Response Relationship, DrugEnzyme ActivationFemaleGlutathioneIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMAP-Kinase-Activated Kinase 2Mitogen-Activated Protein KinasesOxidation-Reductionp38 Mitogen-Activated Protein KinasesPhosphorylationPregnancyProtein Serine-Threonine KinasesAcetylcysteineGlutathioneIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMAP-Kinase-Activated Kinase 2Mitogen-Activated Protein Kinasesp38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesReactive Oxygen SpeciesTumor Necrosis Factor-alpha

Identifiers

PMID11815388
PMCPMC1573138
OpenAlexW2093539580

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.