Evidence map›Paper›PMID 21664694›Full record

ArticleMolecular immunology2011

Leishmania mexicana promastigotes inhibit macrophage IL-12 production via TLR-4 dependent COX-2, iNOS and arginase-1 expression.

Muhannad Shweash, H Adrienne McGachy, Juliane Schroeder, Thikryat Neamatallah, Clare E Bryant, Owain Millington, Jeremy C Mottram, James Alexander, Robin Plevin

Open access · hybridAbstract read
In one paragraph

Article in Molecular immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.0field-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

32 citing papers in PubMed, 58 citations in OpenAlex.

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  6. Human Dendritic Cell Maturation Is Modulated byTropical medicine and infectious disease · 2024
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  7. iScience · 2023
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  9. Frontiers in immunology · 2023
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  10. Unwinding the mechanism of macrophage repolarization potential ofFrontiers in cellular and infection microbiology · 2023
    Article
  11. Article
  12. Visualizing theFrontiers in immunology · 2021
    Review
  13. Giardia lamblia Decreases NF-κB p65Scientific reports · 2020
    Article
  14. Article
  15. Frontiers in microbiology · 2018
    Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Frontiers in immunology · 2017
    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

9 authors at 3 institutions in 1 country.

Muhannad ShweashDivision of Physiology & Pharmacology, Strathclyde Institute for Pharmacy & Biomedical Sciences, 27 Taylor Street, Glasgow G4 0NR, UK.
H Adrienne McGachy
Juliane Schroeder
Thikryat Neamatallah
Clare E Bryant
Owain Millington
Jeremy C Mottram
James Alexander
Robin Plevin
University of Strathclyde · GBUniversity of Cambridge · GBUniversity of Glasgow · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The effects of Leishmania mexicana metacyclic promastigotes upon MAP kinase signalling in mouse bone marrow macrophages and subsequent expression of the disease regulatory proteins iNOS and COX-2 were studied. At a ratio of 5:1, promastigotes caused a marked increase in phosphorylation of the three major MAP kinases, ERK, p38 and JNK. MAP kinase signalling was substantially reduced in TLR-4(-/-) but not TLR-2(-/-) deficient macrophages and completely abolished in double TLR-2/4(-/-) macrophages. A similar outcome was observed using cysteine peptidase B deficient amastigotes. Furthermore, whilst promastigotes had no independent effect on iNOS or COX-2 expression, they prolonged the induction of these proteins stimulated by LPS and enhanced PGE(2) and NO production. Induction of COX-2 and iNOS was also TLR-4 dependent. Blockade of either PGE(2) or NO production with indomethacin or l-NAME reversed promastigote inhibition of LPS induced IL-12 production. Promastigotes also increased macrophage arginase-1 expression and enhanced arginase activity, both of which were substantially reduced in TLR-4 but not TLR-2 deficient macrophages. Surprisingly, arginase inhibition by Nor-NOHA also caused a reversal of promastigote mediated inhibition of macrophage IL-12 production. These data demonstrate for the first time the role of TLR-4 in mediating the effects of L. mexicana promastigotes on MAP kinase activation, up-regulation of COX-2, iNOS as well as arginase-1 expression in macrophages and further shows that PGE(2), NO and arginase activity all contribute substantially to the inhibition of host cell IL-12 production.

Indexed as

AnimalsArginaseBlotting, WesternCyclooxygenase 2Enzyme ActivationExtracellular Signal-Regulated MAP KinasesInterleukin-12Leishmania mexicanaLeishmaniasisMacrophagesMiceNitric Oxide Synthase Type IISignal TransductionToll-Like Receptor 4Arg1 protein, mouseArginaseCyclooxygenase 2Extracellular Signal-Regulated MAP KinasesInterleukin-12Nitric Oxide Synthase Type IITlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID21664694
PMCPMC3173610
OpenAlexW2034215176

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.