Evidence map›Paper›PMID 26567045›Full record

ArticleArthritis research & therapy2015

Anti-inflammatory effects of N-acylethanolamines in rheumatoid arthritis synovial cells are mediated by TRPV1 and TRPA1 in a COX-2 dependent manner.

Torsten Lowin, Martin Apitz, Sven Anders, Rainer H Straub

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 92 citations in OpenAlex.

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  11. The Impact of the CBMolecules (Basel, Switzerland) · 2024
    Review
  12. Article
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  14. Article
  15. Review
  16. Article
  17. Review
  18. Inflammation-the role of TRPA1 channel.Frontiers in physiology · 2023
    Review
  19. Article
  20. Fatty Acid-DerivedNutrients · 2022
    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

4 authors at 1 institution in 1 country.

Torsten LowinLaboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany. torsten.lowin@ukr.de.
Martin ApitzLaboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany. apitzmart@gmail.com.
Sven AndersDepartment of Orthopaedic Surgery, University Hospital Regensburg, Asklepios Clinic Bad Abbach, Kaiser Karl V Allee 3, 93077, Bad Abbach, Germany. s.anders@asklepios.com.
Rainer H StraubLaboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany. rainer.straub@ukr.de.
University Hospital Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe endocannabinoid system modulates function of immune cells and mesenchymal cells such as fibroblasts, which contribute to cartilage destruction in rheumatoid arthritis (RA). The aim of the study was to determine the influence of N-acylethanolamines anandamide (AEA), palmitoylethanolamine (PEA) and oleylethanolamine (OEA) on several features of arthritic inflammation in vitro (human material) and in vivo (a mouse model).

methodsImmunofluorescence and western blotting were used to detect cannabinoid receptors and related enzymes. Cytokines and MMP-3 were measured by ELISA. Intracellular signaling proteins were detected by proteome profiling. Proliferation was quantified by CTB reagent. Adhesion was assessed by the xCELLigence system. After onset of collagen type II arthritis, mice were treated daily with the FAAH inhibitor JNJ1661010 (20 mg/kg) or vehicle.

resultsIL-6, IL-8 and MMP-3 (determined only in synovial fibroblasts (SFs)) were downregulated in primary synoviocytes and SFs of RA and OA after AEA, PEA and OEA treatment. In SFs, this was due to activation of TRPV1 and TRPA1 in a COX-2-dependent fashion. FAAH inhibition increased the efficacy of AEA in primary synoviocytes but not in SFs. The effects of OEA and PEA on SFs were diminished by FAAH inhibition. Adhesion to fibronectin was increased in a CB1-dependent manner by AEA in OASFs. Furthermore, elevation of endocannabinoids ameliorated collagen-induced arthritis in mice.

conclusionsN-acylethanolamines exert anti-inflammatory effects in SFs. A dual FAAH/COX-2 inhibitor, increasing N-acylethanolamine levels with concomitant TRP channel desensitization, might be a good candidate to inhibit the production of proinflammatory mediators of synovial cells and to reduce erosions.

Indexed as

AgedAnimalsAnti-Inflammatory AgentsArthritis, RheumatoidCalcium ChannelsCells, CulturedCyclooxygenase 2Cyclooxygenase 2 InhibitorsDose-Response Relationship, DrugEthanolaminesFemaleHumansInflammation MediatorsMaleMiceMice, Inbred DBAAnti-Inflammatory AgentsCalcium ChannelsCyclooxygenase 2Cyclooxygenase 2 InhibitorsEthanolaminesInflammation MediatorsN-acylethanolaminesNerve Tissue ProteinsPTGS2 protein, humanTransient Receptor Potential ChannelsTRPA1 Cation ChannelTRPA1 protein, humanTRPV1 protein, humanTRPV Cation Channels

Identifiers

PMID26567045
PMCPMC4644337
OpenAlexW2173428397

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.