Evidence map›Paper›PMID 19995978›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis.

Yasuyuki Kihara, Takuya Matsushita, Yoshihiro Kita, Satoshi Uematsu, Shizuo Akira, Jun-ichi Kira, Satoshi Ishii, Takao Shimizu

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

65 citing papers in PubMed, 132 citations in OpenAlex.

  1. Trial
  2. Targeting the HPGDS-PGDSignal transduction and targeted therapy · 2026
    Article
  3. Article
  4. Spatial mapping of the AA-PGEActa neuropathologica · 2025
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  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. FTY720 requires vitamin BCell reports · 2023
    Article
  11. HIV-1 Tat Upregulates TREM1 Expression in Human Microglia.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Article
  12. Article
  13. Update on the pathological roles of prostaglandin ETranslational neurodegeneration · 2023
    Review
  14. The inducible prostaglandin E synthase (mPGES-1) in neuroinflammatory disorders.Experimental biology and medicine (Maywood, N.J.) · 2023
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

5 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 1 country.

Yasuyuki KiharaDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takuya Matsushita
Yoshihiro Kita
Satoshi Uematsu
Shizuo Akira
Jun-ichi Kira
Satoshi Ishii
Takao Shimizu
The University of Tokyo · JPKyushu University · JPOsaka University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The arachidonic acid (AA) cascade produces eicosanoids, such as prostaglandins (PGs), that regulate physiological and pathological functions. Although various nonsteroidal anti-inflammatory drugs have been developed, blocking upstream components (cyclooxygenase-1 and -2) of the AA cascade leads to severe side effects, including gastrointestinal ulcers and cardiovascular events, respectively, due to the complexity of the AA cascade. Here, using an AA cascade-targeted lipidomics approach, we report that microsomal PGE synthase 1 (mPGES-1) plays a key role in experimental autoimmune encephalomyelitis (EAE). Eicosanoids (mainly PGD(2)) are produced constitutively in the spinal cord of naive mice. However, in EAE lesions, the PGE(2) pathway is favored and the PGD(2), PGI(2), and 5-lipoxygenase pathways are attenuated. Furthermore, mPGES-1(-/-) mice showed less severe symptoms of EAE and lower production of IL-17 and IFN-gamma than mPGES-1(+/+) mice. Expression of PGE(2) receptors (EP1, EP2, and EP4) was elevated in EAE lesions and correlated with clinical symptoms. Immunohistochemistry on central nervous systems of EAE mice and multiple sclerosis (MS) patients revealed overt expression of mPGES-1 protein in microglia/macrophages. Thus, the mPGES-1-PGE(2)-EPs axis of the AA cascade may exacerbate EAE pathology. Our findings have important implications for the design of therapies for MS.

Indexed as

LipidsAnimalsArachidonic AcidCytokinesDinoprostoneDisease Models, AnimalHumansImmunohistochemistryIntramolecular OxidoreductasesMiceMice, Inbred C57BLMice, KnockoutMultiple SclerosisProstaglandin-E SynthasesArachidonic AcidCytokinesDinoprostoneIntramolecular OxidoreductasesLipidsProstaglandin-E SynthasesPTGES protein, humanPtges protein, mouse

Identifiers

PMID19995978
PMCPMC2789753
OpenAlexW1981382753

What OpenQuestion holds

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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.