Evidence map›Paper›PMID 39853914›Full record

ArticleImmunity, inflammation and disease2025

TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes.

Christine W Wiger, Trine Ranheim, Henriette Arnesen, Jarle Vaage, Søren E Pischke, Arne Yndestad, Kåre-Olav Stensløkken, May-Kristin Torp

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Article in Immunity, inflammation and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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

8 citing papers in PubMed.

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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

8 authors.

Christine W WigerDivision of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Trine RanheimResearch Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
Henriette ArnesenDivision of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.ORCID 0000-0003-1173-4010
Jarle VaageDivision of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Søren E PischkeInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Arne YndestadResearch Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
Kåre-Olav StensløkkenDivision of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.ORCID 0000-0003-2962-4143
May-Kristin TorpDivision of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Funding

This work was supported by the University of Oslo through the Molecular Life Science (MLS) program.
6 · The paper itself

Abstract

backgroundSepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia-reperfusion.

methodsIsolated C57BL/6N male mouse hearts were perfused for 120 min, with either LPS, E. coli, with and without CLI-095 (TLR4 inhibitor). Primary adult mouse cardiomyocytes were treated with LPS or LPS + CLI-095. Isolated hearts, exposed to 35 min of global ischemia, were treated with either vehicle or CLI-095 during reperfusion. Infarct size was quantified by triphenyltetrazolium staining. Cytokine expression was analyzed with ELISA, western blot analysis, and qPCR.

resultsIn isolated hearts, E. coli increased the expression of proinflammatory cytokines (IL-6 and CXCL2), which was not attenuated with TLR4 inhibition. TLR4 inhibition reduced expression (p = 0.004) and release of IL-6 (p < 0.0001) in LPS-exposed isolated hearts. LPS activated the nuclear-factor κ-light-chain-enhancer of activated B cells signaling pathway (NF-κB) in primary adult cardiomyocytes. Moreover, TLR4 inhibition reduced LPS-induced mRNA expression and release of IL-6 in primary adult cardiomyocytes. Isolated hearts treated with CLI-095 during reperfusion after ischemia (induced DAMPs release) showed reduced infarct size (39 ± 17% to 26 ± 8%, p = 0.034) and decreased IL-6 release (p = 0.006).

conclusionInhibition of TLR4 reduced proinflammatory signaling and cytokine release in LPS-treated and ischemia-reperfused isolated mouse hearts and in primary adult murine cardiomyocytes.

Indexed as

CytokinesHeartMyocytes, CardiacSignal TransductionToll-Like Receptor 4AgingAnimalsCells, CulturedCell SurvivalLipopolysaccharidesMaleMiceMice, Inbred C57BLCytokinesLipopolysaccharidesTlr4 protein, mouseToll-Like Receptor 4DAMPsheartinflammationLPSPAMPssepsis

Identifiers

PMID39853914
PMCPMC11760985

What Socratic holds

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Registered trials

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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 Socratic graph.