Evidence map›Paper›PMID 25451938›Full record

ArticleThe Journal of biological chemistry2015

Extracellular signal-regulated kinase mediates expression of arginase II but not inducible nitric-oxide synthase in lipopolysaccharide-stimulated macrophages.

Yi Jin, Yusen Liu, Leif D Nelin

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Impact of Black Soldier Fly Larvae Oil on Immunometabolic Processes.International journal of molecular sciences · 2025
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  12. Large-Scale Production of Human iPSC-Derived Macrophages for Drug Screening.International journal of molecular sciences · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
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  19. Article
  20. Hypoxic proliferation requires EGFR-mediated ERK activation in human pulmonary microvascular endothelial cells.American journal of physiology. Lung cellular and molecular physiology · 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

3 authors at 1 institution in 1 country.

Yi JinFrom the Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43215.
Yusen LiuFrom the Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43215.
Leif D NelinFrom the Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43215 Leif.Nelin@nationwidechildrens.org.
Nationwide Children's Hospital · US

Funding

Cationic Amino Acid Transporters and Lung NO ProductionR01HL075261 · NHLBI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI NELIN, LEIF D · 2006 to 2010
$1.6M
The Role of MKP-1 in innate immune responses to LPSR01AI068956 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LIU, YUSEN · 2007 to 2010
$1.1M
NHLBI NIH HHS R01 HL075261NHLBI NIH HHS R01HL075261NIAID NIH HHS R01 AI068956NIAID NIH HHS R01AI068956
6 · The paper itself

Abstract

The mitogen-activated protein kinases (MAPK) have been shown to participate in iNOS induction following lipopolysaccharide (LPS) stimulation, while the role of MAPKs in the regulation of arginase remains unclear. We hypothesized that different MAPK family members are involved in iNOS and arginase expression following LPS stimulation. LPS-stimulated RAW 264.7 cells exhibited increased protein and mRNA levels for iNOS, arginase I, and arginase II; although the induction of arginase II was more robust than that for arginase I. A p38 inhibitor completely prevented iNOS expression while it only attenuated arginase II induction. In contrast, a MEK1/2 inhibitor (ERK pathway) completely abolished arginase II expression while actually enhancing iNOS induction in LPS-stimulated cells. Arginase II promoter activity was increased by ∼4-fold following LPS-stimulation, which was prevented by the ERK pathway inhibitor. Arginase II promoter activity was unaffected by a p38 inhibitor or JNK pathway interference. Transfection with a construct expressing a constitutively active RAS mutant increased LPS-induced arginase II promoter activity, while transfection with a vector expressing a dominant negative ERK2 mutant or a vector expressing MKP-3 inhibited the arginase II promoter activity. LPS-stimulated nitric oxide (NO) production was increased following siRNA-mediated knockdown of arginase II and decreased when arginase II was overexpressed. Our results demonstrate that while both the ERK and p38 pathways regulate arginase II induction in LPS-stimulated macrophages, iNOS induction by LPS is dependent on p38 activation. These results suggest that differential inhibition of the MAPK pathway may be a potential therapeutic strategy to regulate macrophage phenotype.

Indexed as

Gene Expression Regulation, EnzymologicAdenoviridaeAnimalsArginaseCell LineCyclic AMPExtracellular Signal-Regulated MAP KinasesHumansLipopolysaccharidesMacrophagesMAP Kinase Signaling SystemMiceNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein KinasesPhenotypePhosphorylationARG2 protein, humanArg2 protein, mouseArginaseCyclic AMPExtracellular Signal-Regulated MAP KinasesLipopolysaccharidesNitric Oxide Synthase Type IINOS2 protein, humanNos2 protein, mousep38 Mitogen-Activated Protein KinasesRNA, Small Interferingc-Jun N-terminal Kinase (JNK)cyclic AMP (cAMP)Macrophage PhenotypeMitogen-activated Protein Kinase (MAPK)p38 MAPKToll-like Receptor 4 (TLR4)

Identifiers

PMID25451938
PMCPMC4303663
OpenAlexW2087694430

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.