Evidence map›Paper›PMID 34754214›Full record

ArticleJournal of inflammation research2021

Linagliptin Inhibits Interleukin-6 Production Through Toll-Like Receptor 4 Complex and Lipopolysaccharide-Binding Protein Independent Pathway in vitro Model.

Hiroshi Saito, Yuya Nakamura, Masahiro Inagaki, Shiho Yamadera, Hideo Misawa, Naoki Sato, Tatsunori Oguchi, Takae Inagaki, Yuya Tsuji, Mayumi Tsuji and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of inflammation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 53% 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

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Review
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

13 authors at 4 institutions in 1 country.

Hiroshi SaitoJA Hiroshima Genneral Hospital, Hatsukaichi City, Hiroshima, Japan.ORCID 0000-0002-5184-9181
Yuya NakamuraDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.ORCID 0000-0002-6156-5975
Masahiro InagakiDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Shiho YamaderaDepartment of Hospital Pharmaceutics, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, Japan.
Hideo MisawaDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Naoki SatoDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Tatsunori OguchiDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Takae InagakiGraduate School of Nursing and Rehabilitation Science, Yokohama City, Kanagawa, Japan.
Yuya TsujiDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Mayumi TsujiDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Isao OhsawaSaiyu Soka Hospital, Soka City, Saitama, Japan.
Hiromichi GotohSaiyu Soka Hospital, Soka City, Saitama, Japan.
Yuji KiuchiDepartment of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.ORCID 0000-0001-7198-3735
Showa University · JPSoka Municipal Hospital · JPHiroshima General Hospital · JPShowa University Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeLipopolysaccharides (LPS) induce inflammation by binding to the Toll-like receptor (TLR) 4 complex, including LPS-binding protein (LBP). The anti-inflammatory effects of linagliptin in LPS-induced inflammation in the TLR4-independent pathway have not been examined before. We examined the anti-inflammatory effects of linagliptin in the TLR4- and the LBP-independent pathway.

methodsU937 cells were cultured in the medium supplemented with 10% fetal bovine serum (FBS) and treated with 100 nM phorbol myristate acetate for 48 h. Cells were then left untreated or were treated with 10 μg/mL anti-TLR4 antibodies alone or in combination with linagliptin for 1 h in media supplemented with or without 10% FBS. The cells were divided into 5 groups: a) control cells (untreated) b) cells treated with LPS c) cells treated with 10 μg/mL anti-TLR4 antibodies d) cells treated with LPS and 10 μg/mL anti-TLR4 antibodies and e) cells treated with LPS, 10 μg/mL anti-TLR4 antibodies, and linagliptin. The LPS concentrations used were 50 pg/mL or 100 pg/mL for cells treated in the presence of 10% FBS and 100 pg/mL or 1 μg/mL for cells treated in the absence of FBS. Linagliptin concentrations of 1 nM, 10 nM, and 100 nM were used for treatment. The supernatants were analyzed for interleukin (IL)-6 production after 24 h of various treatments.

resultsLPS increased IL-6 production compared to the untreated control cells, and anti-TLR4 antibody suppressed LPS-induced increased IL-6 levels. Linagliptin suppressed LPS-induced IL-6 production in a concentration-dependent manner in the presence of FBS. However, only 100 nM linagliptin could suppress LPS-induced IL-6 production in the absence of FBS.

conclusionConcentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment after LPS induction in an experimental model of TLR4 inhibition by anti-TLR4 antibodies. Our results showed that linagliptin may inhibit inflammation through multiple mechanisms centered around the TLR-4-mediated pathway.

Indexed as

anti- toll-like receptor 4 antibodyfetal bovine seruminterleukin-6lipopolysaccharideU937 cells

Identifiers

PMID34754214
PMCPMC8572089
OpenAlexW3208608229

What OpenQuestion holds

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LicenceCC BY-NC
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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.