ArticleImmunology and cell biology2016
β-Adrenergic receptor agonist, compound 49b, inhibits TLR4 signaling pathway in diabetic retina.
Article in Immunology and cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Adrenergic receptors: a key determinant of outcomes in bacterial pneumonia and bacterial sepsis-associated acute lung injury/acute respiratory distress syndrome through participation in pulmonary innate immune response.Frontiers in immunology · 2026Review
- Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases.Frontiers in ophthalmology · 2022Review
- Targeting Novel Regulated Cell Death: Pyroptosis, Necroptosis, and Ferroptosis in Diabetic Retinopathy.Frontiers in cell and developmental biology · 2022Review
- Article
- Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/NF-κB axis repression.Journal of endocrinological investigation · 2021Article
- Loss of TLR4 in endothelial cells but not Müller cells protects the diabetic retina.Experimental eye research · 2021Article
- MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4.Experimental & molecular medicine · 2021Article
- Role of HMGB1 signaling in the inflammatory process in diabetic retinopathy.Cellular signalling · 2020Review
- The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2020Review
- Article
- Bone Morphogenetic Protein-2 Induces Non-Canonical Inflammatory and Oxidative Pathways in Human Retinal Endothelial Cells.Frontiers in immunology · 2020Article
- Glycyrrhizin Protects the Diabetic Retina against Permeability, Neuronal, and Vascular Damage through Anti-Inflammatory Mechanisms.Journal of clinical medicine · 2019Article
- MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4.Experimental and therapeutic medicine · 2018Article
- ATF4 Involvement in TLR4 and LOX-1-Induced Host Inflammatory Response toJournal of ophthalmology · 2018Article
- Toll-like receptor 4 regulates insulin signal transduction in retinal Müller cells.Growth factors (Chur, Switzerland) · 2017Article
- Inhibition of TLR4 alleviates the inflammation and apoptosis of retinal ganglion cells in high glucose.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2017Article
- TLR4 regulates insulin-resistant proteins to increase apoptosis in the mouse retina.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Loss of TLR4 in mouse Müller cells inhibits both MyD88-dependent and -independent signaling.PloS one · 2017Article
- Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1Mediators of inflammation · 2017Article
- Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice.Molecular vision · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Diabetic retinopathy has recently become associated with complications similar to chronic inflammatory diseases. Although it is clear that tumor necrosis factor-α is increased in diabetes, the role of innate immunity is only recently being investigated. As such, we hypothesized that diabetes would increase Toll-like receptor 4 (TLR4) signaling, which could be inhibited by a β-adrenergic receptor agonist (Compound 49b) previously shown to have anti-inflammatory actions. In order to investigate β-adrenergic receptor signaling and TLR4 in the diabetic retina, streptozotocin-injected diabetic mice, as well as human primary retinal endothelial cells (RECs) and rat retinal Müller cells (rMC-1) exposed to high glucose (25 mM), were treated with a novel β-adrenergic receptor agonist, Compound 49b (50 nM), or phosphate-buffered saline (control). TLR4 and its downstream signaling partners (MyD88, IL-1 receptor-associated kinase 1, TNF receptor-associated factor 6 and total and phosphorylated nuclear factor-κB) were examined. In addition, we assessed high-mobility group box 1 (HMGB1) protein levels. Our data showed that diabetes or high-glucose culture conditions significantly increased TLR4 and downstream signaling partners. Compound 49b was able to significantly reduce TLR4 and related molecules in the diabetic animal and retinal cells. HMGB1 was significantly increased in RECs and Müller cells grown in high-glucose culture conditions, which was subsequently reduced with Compound 49b treatment. Our findings suggest that high glucose may increase HMGB1 levels that lead to increased TLR4 signaling. Compound 49b significantly inhibited this pathway, providing a potential mechanism for its protective actions.
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