Evidence map›Paper›PMID 28238855›Full record

ArticleCellular signalling2017

MKP-1 negatively regulates LPS-mediated IL-1β production through p38 activation and HIF-1α expression.

Harvinder Talwar, Christian Bauerfeld, Mohamad Bouhamdan, Pershang Farshi, Yusen Liu, Lobelia Samavati

Erratum issuedAbstract read
In one paragraph

Article in Cellular signalling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

35 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. A review of respirable fine particulate matter (PMFrontiers in molecular neuroscience · 2022
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Harvinder TalwarDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
Christian BauerfeldDepartment of Pediatrics, Division of Critical Care, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
Mohamad BouhamdanDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
Pershang FarshiDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA.
Yusen LiuCenter for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State University College of Medicine, USA.
Lobelia SamavatiDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine and Detroit Medical Center, Detroit, MI 48201, USA; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA. Electronic address: ay6003@wayne.edu.
Wayne State University · USNationwide Children's Hospital · US

Funding

Regulation and Function of Mkp-1 During Sepsis.R01AI124029 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LIU, YUSEN · 2017 to 2021
$1.9M
Role and Regulation of MKP-1 in SarcoidosisR01HL113508 · NHLBI · WAYNE STATE UNIVERSITY · PI SAMAVATI, LOBELIA · 2013 to 2017
$1.9M
NHLBI NIH HHS R01 HL113508NIAID NIH HHS R01 AI124029
6 · The paper itself

Abstract

Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that plays a major role in inflammatory diseases as well as cancer. The inflammatory response after Toll-like receptor (TLR) 4 activation is tightly regulated through phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 preferentially dephosphorylates p38 and JNK. IL-1β is regulated through the activation of MAPK, including p38 as well as several transcription factors. The oxygen-sensitive transcription factor HIF-1α is a known transcription factor for several inflammatory cytokines including IL-1β and IL-6. Here, we report that MKP-1 regulates HIF-1α expression in response to LPS. MKP-1 deficient bone marrow derived macrophages (BMDMs) exhibited increased reactive oxygen species (ROS) production and higher HIF-1α expression. In contrast, the expression of all three isoforms of prolyl hydroxylases (PHDs), which are important in destabilizing HIF-1α through hydroxylation, were significantly decreased in MKP-1 deficient BMDMs. LPS challenge of MKP-1 deficient BMDMs led to a substantial increase in IL-1β production. An inhibitor of HIF-1α significantly decreased LPS mediated IL-1β production both at the transcript and protein levels. Similarly, inhibition of p38 MAP kinase reduced LPS mediated pro-IL-1β and HIF-1α protein levels as well as ROS production in MKP-1 deficient BMDMs. These findings demonstrate a regulatory function for MKP-1 in modulating IL-1β expression through p38 activation, ROS production and HIF-1α expression.

Indexed as

AnimalsAnthracenesDual Specificity Phosphatase 1EchinomycinGene Expression RegulationHypoxia-Inducible Factor 1, alpha SubunitInterleukin-1betaInterleukin-6JNK Mitogen-Activated Protein KinasesLipopolysaccharidesMacrophagesMicep38 Mitogen-Activated Protein KinasesPhosphorylationReactive Oxygen SpeciesAnthracenesDual Specificity Phosphatase 1Dusp1 protein, mouseEchinomycinHypoxia-Inducible Factor 1, alpha SubunitInterleukin-1betaInterleukin-6JNK Mitogen-Activated Protein KinasesLipopolysaccharidesp38 Mitogen-Activated Protein KinasespyrazolanthroneReactive Oxygen SpeciesBMDMsDUSPsHIF-1 αIL-1βMacrophagesMKP-1p38

Identifiers

PMID28238855
PMCPMC5410178
OpenAlexW2589478819

What OpenQuestion holds

Textmetadata
LicenceTDM
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.