ArticleAnesthesiology2014
Toll-like receptor 4 is essential to preserving cardiac function and survival in low-grade polymicrobial sepsis.
Article in Anesthesiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- MicroRNAs as regulators of cardiac dysfunction in sepsis: pathogenesis and diagnostic potential.Frontiers in cardiovascular medicine · 2025Pooled it
- A developmentally informed narrative review of Toll-like receptors in adult and pediatric acute respiratory distress syndrome.Annals of translational medicine · 2026Review
- Phosphorylated toll-like receptor 4 defines a high-risk sepsis endotype.Critical care (London, England) · 2026Article
- Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.Journal of cellular and molecular medicine · 2024Article
- Mycobacterium bovis BCG increase the selected determinants of monocyte/macrophage activity, which were diminished in response to gastric pathogen Helicobacter pylori.Scientific reports · 2023Article
- Sex-specific differences in cardiac function, inflammation and injury during early polymicrobial sepsis.Intensive care medicine experimental · 2022Article
- Article
- Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction.Bioengineered · 2021Article
- Targeting Toll-Like Receptors in Sepsis: From Bench to Clinical Trials.Antioxidants & redox signaling · 2021Review
- Anti-inflammatory effects of microRNA-223 on sepsis-induced lung injury in rats by targeting the Toll-like receptor signaling pathway.Experimental and therapeutic medicine · 2021Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Respiratory syncytial virus infection of microglia exacerbates SH-SY5Y neuronal cell injury by inducing the secretion of inflammatory cytokines: A TranswellIranian journal of basic medical sciences · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- C23, an oligopeptide derived from cold-inducible RNA-binding protein, suppresses inflammation and reduces lung injury in neonatal sepsis.Journal of pediatric surgery · 2019Article
- MicroRNA-494-3p protects rat cardiomyocytes against septic shock via PTEN.Experimental and therapeutic medicine · 2019Article
- miR-25 inhibits sepsis-induced cardiomyocyte apoptosis by targetting PTEN.Bioscience reports · 2018Article
- A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.Scientific reports · 2018Article
- Experimental Study of the Protective Effect of Simvastatin on Lung Injury in Rats with Sepsis.Inflammation · 2018Article
- Toll-like receptor 4-induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum CaThe Journal of biological chemistry · 2018Article
- The Central Role of the Inflammatory Response in Understanding the Heterogeneity of Sepsis-3.BioMed research international · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundToll-like receptor 4 (TLR4), the receptor for endotoxin, mediates hyperinflammatory response and contributes to high mortality during both endotoxin shock and severe sepsis. However, little is known about the role of TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often associated with immunosuppression.
methodsLow-grade polymicrobial sepsis was generated by cecum ligation and puncture. Mortality was monitored in wild- type (C57BL/10ScSn) and TLR4def (C57BL/10ScCr) mice. Ex vivo heart and individual cardiomyocyte function were assessed in Langendorff (Hugo Sachs Elektronik; Harvard Apparatus, Holliston, MA) and IonOptix systems (IonOptix, Milton, MA), respectively. Serum chemistry was tested for liver and kidney injury. Cytokines were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic functions were assessed using flow cytometry. Reactive oxygen species were measured using redox-sensitive dichlorodihydrofluorescein dye.
resultsFollowing cecum ligation and puncture, wild-type mice developed bacterial peritonitis with mild cardiac dysfunction (n=3 in sham and n=8 in cecum ligation and puncture) and a mortality of 23% within 14 days (n=22). In comparison, septic TLR4def mice had deleterious cardiac dysfunction (n=6 in sham and n=10 in cecum ligation and puncture), kidney and liver injury (n=7), and much higher mortality at 81% (n=21). The deleterious effects observed in septic TLR4def mice were associated with increased local and systemic cytokine response, reduced neutrophil migratory and phagocytic function, increased reactive oxygen species generation in leukocytes, and impaired bacterial clearance.
conclusionTLR4 plays an essential role in host defense against low-grade polymicrobial sepsis by mediating neutrophil migratory/phagocytic functions, attenuating inflammation, reducing reactive oxygen species generation, and enhanced bacterial clearance.
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