Evidence map›Paper›PMID 25077631›Full record

ArticlePloS one2014

Macrophage-activating lipopeptide-2 requires Mal and PI3K for efficient induction of heme oxygenase-1.

Xiaoxing You, Liangzhuan Liu, Yanhua Zeng, Ranhui Li, Jun He, Xiaohua Ma, Chuanhao Jiang, Cuiming Zhu, Liesong Chen, Minjun Yu and 2 more

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact, top 93% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Immune Evasion ofInternational journal of molecular sciences · 2024
    Review
  3. Review
  4. Antioxidants (Basel, Switzerland) · 2021
    Article
  5. TIRAP in the Mechanism of Inflammation.Frontiers in immunology · 2021
    Review
  6. Frontiers in microbiology · 2020
    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

12 authors at 1 institution in 1 country.

Xiaoxing YouInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Liangzhuan LiuInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Yanhua ZengInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Ranhui LiInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Jun HeInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China; Department of Clinical Laboratory, The Affiliated Nanhua Hospital of University of South China, Hengyang City, P.R. China.
Xiaohua MaInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China; Department of Clinical Laboratory, Changsha Central Hospital, Chagnsha City, P.R. China.
Chuanhao JiangInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Cuiming ZhuInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Liesong ChenInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Minjun YuInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Guangli OuInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
Yimou WuInstitution of Pathogenic Biology, Medical College, University of South China, Hengyang City, P.R. China.
University of South China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis study is to investigate the mechanisms by which macrophage-activating lipopeptide-2 (MALP-2) induces heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme, in human monocytes.

methodsHuman monocytic THP-1 cells were cultured for transient transfection with plasmids and stimulation with MALP-2 for indicative time intervals. After incubation with MALP-2, cells were collected and disrupted, before being tested for promoter activity using luciferase assay. For analysis of proteins, immunoreactive bands were detected using an enhanced chemiluminescence Western blotting system, and the band intensity was measured by densitometryic analysis. For the detection of co-immunoprecipitation, SDS-PAGE was performed and the membranes were probed using respective antibodies. To investigate the cellular localization of NF-E2-related factor 2 (Nrf2), cells underwent immunofluorescence staining and confocal microscopy, and were analyzed using electrophoretic mobility shift assay.

resultsMALP-2-induced HO-1 expression and promoter activity were abrogated by transfection with dominant negative (DN) plasmids of TLR2 and TLR6, or their neutralizing antibodies. However, inhibition of MyD88 or transfection with the DN-MyD88 was insufficient to attenuate HO-1 expression. In contrast, mutation or silencing of MyD88 adapter-like (Mal) by DN-Mal or siRNA almost completely blocked HO-1 induction. Btk, c-Src and PI3K were also involved in MALP-2-induced HO-1 expression, as revealed by specific inhibitors LFM-A13, PP1 and LY294002, or by transfection with siRNA of c-Src. MALP-2-induced activation of PI3K was attenuated by transfection with DN mutant of Mal, and by pretreatment with LFM-A13 or PP1. Furthermore, MALP-2 stimulated the translocation of Nrf2 from the cytosol to the nucleus and Nrf2 binding to the ARE site in the HO-1 promoter, which could also be inhibited by pretreatment with a PI3K inhibitor, LY294002.

conclusionsThese results indicated that MALP-2 required TLR2/6, Btk, Mal and c-Src to activate PI3K, which in turn initiated the activation of Nrf2 for efficient HO-1 induction.

Indexed as

Cell LineEnzyme InductionHeme Oxygenase-1HumansLipopeptidesPhosphatidylinositol 3-KinasesToll-Like ReceptorsHeme Oxygenase-1Lipopeptidesmacrophage stimulatory lipopeptide 2Phosphatidylinositol 3-KinasesToll-Like Receptors

Identifiers

PMID25077631
PMCPMC4117634
OpenAlexW1999093241

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.