ArticleScientific reports2020
TAK-242, a specific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-induced skeletal muscle wasting in mice.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95 citing papers in PubMed, 147 citations in OpenAlex.
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- A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells.bioRxiv : the preprint server for biology · 2026Article
- Article
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- Vitamin B3 rescues mitochondrial homeostasis in dexamethasone-induced skeletal muscle atrophy by reducing oxidative stress.Journal of bioenergetics and biomembranes · 2026Article
- Wzc mutation enhances virulence in CRKP ST11-KL64 via complement-mediated lysis and lipopolysaccharide release.Microbiology spectrum · 2026Article
- Optimization of Preclinical Rodent Research Models of Human Shock: Part One Intra-Abdominal Sepsis.Shock (Augusta, Ga.) · 2026Review
- Microglial Lyn Kinase-TRPV4 axis mediates social deficits in a maternal immune activation model.Journal of neuroinflammation · 2026Article
- Antibiotics modulate Escherichia coli-derived bacterial extracellular vesicle production and their upregulation of ICAM-1 in human endothelial cells.Biology open · 2026Article
- Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling.Investigative ophthalmology & visual science · 2026Article
- Peptide OH-CATH30 Mitigates Cachexia-Induced Muscle Atrophy via Modulation of TLR4-Associated Inflammation.Journal of cachexia, sarcopenia and muscle · 2026Article
- Sepsis-associated skeletal muscle wasting is ameliorated by pharmacological inhibition of the STAT3 signaling pathway in mice.Scientific reports · 2026Article
- Transcending aging: disease specificity, assessment challenges, and management strategies for rheumatoid arthritis-related sarcopenia.Frontiers in medicine · 2026Review
- TLR4 mediates post-traumatic depression via kynurenine pathway activation in a murine traumatic brain injury model.Frontiers in pharmacology · 2026Article
- Beyond muscle weakness: pathogenesis of sepsis-induced myopathy and its management.Open medicine (Warsaw, Poland) · 2026Review
- Pathogenesis and intervention strategies for metabolic dysfunction-associated fatty liver disease from the perspective of the gut-microbiota-liver axis.Frontiers in immunology · 2026Review
- Oridonin attenuates TLR4-driven inflammation and autophagy in LPS-stimulated enteric glial cells: anFrontiers in cellular neuroscience · 2026Article
- Surface Calcium Enrichment of Biogenic Hydroxyapatite Regulates Macrophage Inflammation via Toll-Like Receptor 4 Signaling.Biomaterials research · 2026Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or various endogenous diseases related to bacterial translocation from the gut. Systemic inflammatory responses induced by endotoxemia induce severe involuntary loss of skeletal muscle, termed muscle wasting, which adversely affects the survival and functional outcomes of these patients. Currently, no drugs are available for the treatment of endotoxemia-induced skeletal muscle wasting. Here, we tested the effects of TAK-242, a Toll-like receptor 4 (TLR4)-specific signalling inhibitor, on myotube atrophy in vitro and muscle wasting in vivo induced by endotoxin. LPS treatment of murine C2C12 myotubes induced an inflammatory response (increased nuclear factor-κB activity and interleukin-6 and tumour necrosis factor-α expression) and activated the ubiquitin-proteasome and autophagy proteolytic pathways (increased atrogin-1/MAFbx, MuRF1, and LC-II expression), resulting in myotube atrophy. In mice, LPS injection increased the same inflammatory and proteolytic pathways in skeletal muscle and induced atrophy, resulting in reduced grip strength. Notably, pretreatment of cells or mice with TAK-242 reduced or reversed all the detrimental effects of LPS in vitro and in vivo. Collectively, our results indicate that pharmacological inhibition of TLR4 signalling may be a novel therapeutic intervention for endotoxemia-induced muscle wasting.
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