ArticleCellular and molecular life sciences : CMLS2018
An MD2-derived peptide promotes LPS aggregation, facilitates its internalization in THP-1 cells, and inhibits LPS-induced pro-inflammatory responses.
Article in Cellular and molecular life sciences : CMLS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Liver as a key organ for systemic antimicrobial defense.Hepatology communications · 2025Review
- The Overlapping Biology of Sepsis and Cancer and Therapeutic Implications.Biomedicines · 2025Review
- Innovative Strategies and Methodologies in Antimicrobial Peptide Design.Journal of functional biomaterials · 2024Review
- Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma.Translational cancer research · 2024Article
- Targeting NF-κB Signaling: Selected Small Molecules Downregulate Pro-Inflammatory Cytokines in Both Food Allergen and LPS-Induced Inflammation.International journal of molecular sciences · 2024Article
- Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications.Journal of functional biomaterials · 2023Review
- Role of Anti-Cancer Peptides as Immunomodulatory Agents: Potential and Design Strategy.Pharmaceutics · 2022Review
- MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABAJournal of neuroinflammation · 2021Article
- MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway.Journal of gastrointestinal oncology · 2021Article
- Ethyl 2-Succinate-Anthraquinone Attenuates Inflammatory Response and Oxidative Stress via Regulating NLRP3 Signaling Pathway.Frontiers in pharmacology · 2021Article
- Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis.International journal of biological sciences · 2020Article
- Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4.Cellular and molecular life sciences : CMLS · 2019Article
- The Understanding and Management of Organism Toxicity in Septic Shock.Journal of innate immunity · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS. An MD54 analog of the same size was also designed in which a leucine residue at a heptadic position was replaced with an alanine residue. MD54 but not its analog, MMD54 induced aggregation of LPS and aided in its internalization within THP-1 monocytes. Furthermore, MD54 inhibited LPS-induced nuclear translocation of NF-κB in PMA-treated THP-1 and TLR4/MD2/CD14-transfected HEK-293T cells and the production of pro-inflammatory cytokines. In addition, in in vivo experiments, MD54 showed marked protection and survival of mice against LPS-induced inflammation and death. Overall, we have identified a short peptide with heptad repeat sequence from MD2 that can cause aggregation of LPS and abet in its internalization within THP-1 cells, resulting in attenuation of LPS-induced pro-inflammatory responses in vitro and in vivo.
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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.