ArticleOxidative medicine and cellular longevity2015
Toll-Like Receptor 4 Promotes NO Synthesis by Upregulating GCHI Expression under Oxidative Stress Conditions in Sheep Monocytes/Macrophages.
Article in Oxidative medicine and cellular longevity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review.Frontiers in immunology · 2024Pooled it
- Oxidative stress-driven disease-associated microglia (DAM)-like polarization in human microglia (HMC3) cells exposed to small-size silver nanoparticles in a transwell co-culture system with neurons (cholinergic differentiated SH-SY5Y) cells in vitro.Archives of toxicology · 2026Article
- Macroalgae-Inspired Brominated Chalcones as Cosmetic Ingredients with the Potential to Target Skin Inflammaging.Marine drugs · 2025Article
- Effects of Goji Berry Supplementation on Immune-Related and Antioxidant Gene Expression in the Male Rabbit Reproductive Tract.Animals : an open access journal from MDPI · 2025Article
- Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injuryFrontiers in cell and developmental biology · 2022Article
- Overexpression of Toll-like receptor 4 contributes to the internalization and elimination of Escherichia coli in sheep by enhancing caveolae-dependent endocytosis.Journal of animal science and biotechnology · 2021Article
- Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV.Cardiovascular research · 2021Article
- Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism.Frontiers in neuroscience · 2021Review
- Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress.Frontiers in cellular and infection microbiology · 2021Review
- Melatonin Ameliorates Inflammation and Oxidative Stress by Suppressing the p38MAPK Signaling Pathway in LPS-Induced Sheep Orchitis.Antioxidants (Basel, Switzerland) · 2020Article
- Evaluating the effect ofJournal of biological research (Thessalonike, Greece) · 2020Article
- Overexpression of Toll-Like Receptor 4 Affects Autophagy, Oxidative Stress, and Inflammatory Responses in Monocytes of Transgenic Sheep.Frontiers in cell and developmental biology · 2020Article
- Review
- Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Overexpression of Toll-like Receptor 4-linked Mitogen-activated Protein Kinase Signaling Contributes to Internalization ofInternational journal of biological sciences · 2018Article
- Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction, oxidative stress markers, and sperm parameters in response to bacterial lipopolysaccharide in infertile men.Journal of assisted reproduction and genetics · 2017Article
- Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes.Scientific reports · 2016Article
- Repeated lipopolysaccharide exposure causes corticosteroid insensitive airway inflammation via activation of phosphoinositide-3-kinase δ pathway.Biochemistry and biophysics reports · 2016Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many groups of Gram-negative bacteria cause diseases that are harmful to sheep. Toll-like receptor 4 (TLR4), which is critical for detecting Gram-negative bacteria by the innate immune system, is activated by lipopolysaccharide (LPS) to initiate inflammatory responses and oxidative stress. Oxidation intermediates are essential activators of oxidative stress, as low levels of free radicals form a stressful oxidative environment that can clear invading pathogens. NO is an oxidation intermediate and its generation is regulated by nitric oxide synthase (iNOS). Guanosine triphosphate cyclohydrolase (GCHI) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, which is essential for the production of inducible iNOS. Previously, we made vectors to overexpress the sheep TLR4 gene. Herein, first generation (G1) of transgenic sheep was stimulated with LPS in vivo and in vitro, and oxidative stress and GCHI expression were investigated. Oxidative injury caused by TLR4 overexpression was tightly regulated in tissues. However, the transgenic (Tg) group still secreted nitric oxide (NO) when an iNOS inhibitor was added. Furthermore, GCHI expression remained upregulated in both serum and monocytes/macrophages. Thus, overexpression of TLR4 in transgenic sheep might accelerate the clearance of invading microbes through NO generation following LPS stimulation. Additionally, TLR4 overexpression also enhances GCHI activation.
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