ArticleBritish journal of pharmacology2013
Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 66 citations in OpenAlex.
- Therapeutic Effects of Propolis Supplementation on the Inflammatory State, Oxidative Stress, and Uremic Toxins in dialysis Patients: A Systematic Review.Food science & nutrition · 2026Review
- STING COPII ER Export Trafficking and Signaling Primed by Phosphorylation Switches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis.Rheumatology (Oxford, England) · 2024Review
- Immunohistochemical Localization of MD2, a Co-Receptor of TLR4, in the Adult Mouse Brain.ACS chemical neuroscience · 2023Article
- Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease.Frontiers in endocrinology · 2023Review
- Article
- Bioinformatics analysis of potential key genes and pathways in neonatal necrotizing enterocolitis.BMC pediatrics · 2022Article
- Allergic Inflammation: Effect of Propolis and Its Flavonoids.Molecules (Basel, Switzerland) · 2022Review
- Pharmacologic therapies of ARDS: From natural herb to nanomedicine.Frontiers in pharmacology · 2022Review
- Molecular and cellular mechanisms of the effects of Propolis in inflammation, oxidative stress and glycemic control in chronic diseases.Nutrition & metabolism · 2020Article
- Development of a Highly Efficient Hybrid Peptide That Increases Immunomodulatory Activity Via the TLR4-Mediated Nuclear Factor-κB Signaling Pathway.International journal of molecular sciences · 2019Article
- Tannic acid prevents macrophage-induced pro-fibrotic response in lung epithelial cells via suppressing TLR4-mediated macrophage polarization.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway.International journal of molecular sciences · 2018Review
- Toll-Like Receptor-4 Signaling Drives Persistent Fibroblast Activation and Prevents Fibrosis Resolution in Scleroderma.Advances in wound care · 2017Review
- Targeting myeloid differentiation protein 2 by the new chalcone L2H21 protects LPS-induced acute lung injury.Journal of cellular and molecular medicine · 2017Article
- Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout.Scientific reports · 2016Article
- Computational Approaches to Toll-Like Receptor 4 Modulation.Molecules (Basel, Switzerland) · 2016Review
- Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury.Scientific reports · 2016Article
- MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis.British journal of pharmacology · 2015Article
- Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.Molecular medicine reports · 2015Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeToll-like receptors (TLRs) play a crucial role in recognizing invading pathogens and endogenous danger signal to induce immune and inflammatory responses. Since dysregulation of TLRs enhances the risk of immune disorders and chronic inflammatory diseases, modulation of TLR activity by phytochemicals could be useful therapeutically. We investigated the effect of caffeic acid phenethyl ester (CAPE) on TLR-mediated inflammation and the underlying regulatory mechanism. EXPERIMENTAL APPROACH: Inhibitory effects of CAPE on TLR4 activation were assessed with in vivo murine skin inflammation model and in vitro production of inflammatory mediators in macrophages. In vitro binding assay, cell-based immunoprecipitation study and liquid chromatography-tandem mass spectrometry analysis were performed to determine lipopolysaccharide (LPS) binding to MD2 and to identify the direct binding site of CAPE in MD2. KEY
resultsTopical application of CAPE attenuated dermal inflammation and oedema induced by intradermal injection of LPS (a TLR4 agonist). CAPE suppressed production of inflammatory mediators and activation of NFκB and interferon-regulatory factor 3 (IRF3) in macrophages stimulated with LPS. CAPE interrupted LPS binding to MD2 through formation of adduct specifically with Cys133 located in hydrophobic pocket of MD2. The inhibitory effect on LPS-induced IRF3 activation by CAPE was not observed when 293T cells were reconstituted with MD2 (C133S) mutant. CONCLUSIONS AND IMPLICATIONS: Our results show a novel mechanism for anti-inflammatory activity of CAPE to prevent TLR4 activation by interfering with interaction between ligand (LPS) and receptor complex (TLR4/MD2). These further provide beneficial information for the development of therapeutic strategies to prevent chronic inflammatory diseases.
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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.