Evidence map›Paper›PMID 25539811›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6.

Shuwei Qiu, Yimin Feng, Gene LeSage, Ying Zhang, Charles Stuart, Lei He, Yi Li, Yi Caudle, Ying Peng, Deling Yin

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

49 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Interactive effects of morphine and the HIV integrase inhibitor, cabotegravir, in male and female mice.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
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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

10 authors.

Shuwei QiuDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and.
Yimin FengDepartment of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and.
Gene LeSageDepartment of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and.
Ying ZhangDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205.
Charles StuartDepartment of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and.
Lei HeDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;
Yi LiDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;
Yi CaudleDepartment of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and.
Ying PengDepartment of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; yin@etsu.edu 2353352460@qq.com.
Deling YinDepartment of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614; and yin@etsu.edu 2353352460@qq.com.

Funding

ROLE OF OPIOIDS SIGNALING IN IMMUNE SUPPRESSIONR15DA020120 · NIDA · EAST TENNESSEE STATE UNIVERSITY · PI YIN, DELING · 2005 to 2011
$859k
Role of Toll-Like Receptor 4 Signaling in Stress-Induced Lymphocyte ApoptosisR15GM094740 · NIGMS · EAST TENNESSEE STATE UNIVERSITY · PI YIN, DELING · 2011 to 2011
$321k
NIDA NIH HHS R15 DA020120NIGMS NIH HHS R15 GM094740PHS HHS NIDA020120PHS HHS NIGM094740
6 · The paper itself

Abstract

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. TLRs and acetylcholine are widely expressed in the immune and nervous systems, and play critical roles in immune responses. In this article, we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages through differential regulation of TLRs and acetylcholinesterase. Either morphine or inhibition of acetylcholine significantly promotes upregulation of microRNA-124 (miR-124) in microglia, bone marrow-derived macrophages, and the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-κB p65 and TNFR-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, whereas p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently upregulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression, which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia.

Indexed as

RNA Interference3' Untranslated RegionsAnimalsBase PairingBase SequenceBinding SitesCell LineGene Expression RegulationHumansImmunity, InnateImmunomodulationMaleMiceMicrogliaMicroRNAsMorphine3' Untranslated RegionsMicroRNAsMirn124 microRNA, mouseMorphineTNF Receptor-Associated Factor 6Transcription Factor RelA

Identifiers

PMID25539811
PMCPMC4297711

What OpenQuestion holds

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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.