ArticleCells2023
TLR4 Overexpression Aggravates Bacterial Lipopolysaccharide-Induced Apoptosis via Excessive Autophagy and NF-κB/MAPK Signaling in Transgenic Mammal Models.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
The trial behind it
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
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- Autophagy as a Proposed Regulatory Interface in the Gut Microbiota-Cardiovascular Axis.Journal of inflammation research · 2026Review
- The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Research progress on targeting autophagy pathways with medicinal plants and their active metabolites for the treatment of heart failure.Frontiers in pharmacology · 2026Review
- Gut microbiota in asthma: mechanisms, clinical evidence, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Pinostrobin Inhibits Nuclear Factor-Kappa B Signaling and Production of Inflammatory Cytokines and Chemokines in Human Macrophages.Nutrients · 2025Article
- The Effect of Lipopolysaccharide on Anxiety Levels in Rats Exposed to Chronic Unpredictable Mild Stress of Varying Duration.Bulletin of experimental biology and medicine · 2025Article
- Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025Review
- Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes.International journal of molecular sciences · 2025Review
- Effects of Modified Attapulgite on Daily Weight Gain, Serum Indexes and Serum Metabolites in Fattening Beef Cattle.Animals : an open access journal from MDPI · 2025Article
- Xanthine Derivative KMUP-3 Alleviates Periodontal Bone Resorption by Inhibiting Osteoclastogenesis and Macrophage Pyroptosis.Journal of periodontal research · 2025Article
- Porphyromonas gingivalis aggravates atherosclerotic plaque instability by promoting lipid-laden macrophage necroptosis.Signal transduction and targeted therapy · 2025Article
- Carbonate Buffer Mixture Alleviates Subacute Rumen Acidosis Induced by Long-Term High-Concentrate Feeding in Dairy Goats by Regulating Rumen Microbiota.Microorganisms · 2025Article
- Linalool combatseLife · 2025Article
- MicroRNA warfare: how chickens combatFrontiers in cellular and infection microbiology · 2025Article
- Advances in gut-lung axis research: clinical perspectives on pneumonia prevention and treatment.Frontiers in immunology · 2025Review
- TLR4 signalling in ischemia/reperfusion injury: a promising target for linking inflammation, oxidative stress and programmed cell death to improve organ transplantation outcomes.Frontiers in immunology · 2024Review
- Editorial: Novelties in acute myeloid leukemia: from biology to clinical applications.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Gram-negative bacterial infections pose a significant threat to public health. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and induces innate immune responses, autophagy, and cell death, which have major impacts on the body's physiological homeostasis. However, the role of TLR4 in bacterial LPS-induced autophagy and apoptosis in large mammals, which are closer to humans than rodents in many physiological characteristics, remains unknown. So far, few reports focus on the relationship between TLR, autophagy, and apoptosis in large mammal levels, and we urgently need more tools to further explore their crosstalk. Here, we generated a TLR4-enriched mammal model (sheep) and found that a high-dose LPS treatment blocked autophagic degradation and caused strong innate immune responses and severe apoptosis in monocytes/macrophages of transgenic offspring. Excessive accumulation of autophagosomes/autolysosomes might contribute to LPS-induced apoptosis in monocytes/macrophages of transgenic animals. Further study demonstrated that inhibiting TLR4 downstream NF-κB or p38 MAPK signaling pathways reversed the LPS-induced autophagy activity and apoptosis. These results indicate that the elevated TLR4 aggravates LPS-induced monocytes/macrophages apoptosis by leading to lysosomal dysfunction and impaired autophagic flux, which is associated with TLR4 downstream NF-κB and MAPK signaling pathways. This study provides a novel TLR4-enriched mammal model to study its potential effects on autophagy activity, inflammation, oxidative stress, and cell death. These findings also enrich the biological functions of TLR4 and provide powerful evidence for bacterial infection.
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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.