Evidence map›Paper›PMID 33820486›Full record

ArticleRenal failure2021

Inhibitory effect of anti-malarial agents on the expression of proinflammatory chemokines via Toll-like receptor 3 signaling in human glomerular endothelial cells.

Riko Sato, Tadaatsu Imaizumi, Tomomi Aizawa, Shojiro Watanabe, Koji Tsugawa, Shogo Kawaguchi, Kazuhiko Seya, Tomoh Matsumiya, Hiroshi Tanaka

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Renal failure, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05947812 (A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 33% 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.

NCT05947812 phase2unknown statusnot on this mapstarted 2023, after this paper: background citation

A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression (the "ACLR8-LR" Study)

TypeinterventionalSponsor60P Australia Pty LtdRan2023 to 2024Enrolled148ConditionsCOVID 19 Disease, Mild to Moderate COVID 19 Disease, SARS-CoV-2, Infectious DiseaseArmsTafenoquine Oral Tablet, Placebo
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Type I IFN in Glomerular Disease: Scarring beyond the STING.International journal of molecular sciences · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. 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

9 authors at 2 institutions in 1 country.

Riko SatoDepartment of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
Tadaatsu ImaizumiDepartment of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Tomomi AizawaDepartment of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
Shojiro WatanabeDepartment of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
Koji TsugawaDepartment of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
Shogo KawaguchiDepartment of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Kazuhiko SeyaDepartment of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Tomoh MatsumiyaDepartment of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hiroshi TanakaDepartment of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
Hirosaki University Hospital · JPHirosaki University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAlthough anti-malarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the treatment of systemic lupus erythematosus, their efficacy for lupus nephritis (LN) remains unclear. Given that upregulation of glomerular Toll-like receptor 3 (TLR3) signaling plays a pivotal role in the pathogenesis of LN, we examined whether CQ and HCQ affect the expression of the TLR3 signaling-induced representative proinflammatory chemokines, monocyte chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5) in cultured human glomerular endothelial cells (GECs).

methodsWe examined the effect of polyinosinic-polycytidylic acid (poly IC), an agonist of TLR3, on MCP-1, CCL5 and interferon (IFN)-β expression in GECs. We then analyzed whether pretreatment with CQ, HCQ, or dexamethasone (DEX) inhibits poly IC-induced expression of these chemokines using real-time quantitative reverse transcriptase PCR and ELISA. Phosphorylation of signal transducers and activator of transcription protein 1 (STAT1) was examined using western blotting.

resultsPoly IC increased MCP-1 and CCL5 expression in a time- and concentration-dependent manner in GECs. Pretreating cells with CQ, but not DEX, attenuated poly IC-induced MCP-1 and CCL5 expression; however, HCQ pretreatment attenuated poly IC-induced CCL5, but not MCP-1. HCQ did not affect the expression of IFN-β and phosphorylation of STAT-1.

conclusionConsidering that TLR3 signaling is implicated, at least in part, in LN pathogenesis, our results suggest that anti-malarial agents exert a protective effect against the development of inflammation in GECs, as postulated in LN. Interestingly, CQ is a rather powerful inhibitor compared with HCQ on TLR3 signaling-induced chemokine expression in GECs. In turn, these findings may further support the theory that the use of HCQ is safer than CQ in a clinical setting. However, further detailed studies are needed to confirm our preliminary findings.

Indexed as

AntimalarialsCell LineCells, CulturedChemokine CCL5ChemokinesChloroquineEndothelial CellsHumansInflammationInterferon-betaKidney GlomerulusLupus NephritisPoly I-CSignal TransductionToll-Like Receptor 3AntimalarialsChemokine CCL5ChemokinesChloroquineInterferon-betaPoly I-CTLR3 protein, humanToll-Like Receptor 3Chloroquineglomerular endothelial cellshydroxychloroquinelupus nephritisToll-like receptor 3

Identifiers

PMID33820486
PMCPMC8032345
OpenAlexW3147737351

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.