ArticleJournal of leukocyte biology2015
Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways.
Article in Journal of leukocyte biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- The macrocyclic peptide rhesus theta defensin 1 activates interferon and antiviral pathways in human monocytes.Journal of leukocyte biology · 2025Article
- Review
- Porcine beta defensin 2 attenuates inflammatory responses in IPEC-J2 cells against Escherichia coli via TLRs-NF-κB/MAPK signaling pathway.BMC veterinary research · 2024Article
- Native and Engineered Cyclic Disulfide-Rich Peptides as Drug Leads.Molecules (Basel, Switzerland) · 2023Review
- Inhibition of miR-146a Expression and Regulation of Endotoxin Tolerance by Rhesus Theta-Defensin-1.Mediators of inflammation · 2023Article
- A Fun-Guide to Innate Immune Responses to Fungal Infections.Journal of fungi (Basel, Switzerland) · 2022Review
- Preclinical Pharmacokinetics and Safety of Intravenous RTD-1.Antimicrobial agents and chemotherapy · 2022Article
- Theta-Defensins to Counter COVID-19 as Furin Inhibitors:Computational and mathematical methods in medicine · 2022Article
- A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections.Scientific reports · 2021Article
- Anti-Inflammatory Effects of RTD-1 in a Murine Model of ChronicAntibiotics (Basel, Switzerland) · 2021Article
- Host Defense Peptides as Templates for Antifungal Drug Development.Journal of fungi (Basel, Switzerland) · 2020Review
- Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-BioMed research international · 2020Article
- RTD-1 therapeutically normalizes synovial gene signatures in rat autoimmune arthritis and suppresses proinflammatory mediators in RA synovial fibroblasts.Physiological genomics · 2019Article
- Modulation of toll-like receptor signaling by antimicrobial peptides.Seminars in cell & developmental biology · 2019Review
- Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein-protein interactions.The Biochemical journal · 2019Review
- Porcine Beta-Defensin 2 Provides Protection Against Bacterial Infection by a Direct Bactericidal Activity and Alleviates Inflammation via Interference With the TLR4/NF-κB Pathway.Frontiers in immunology · 2019Article
- Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species.Antimicrobial agents and chemotherapy · 2018Article
- In-cell production of a genetically-encoded library based on the θ-defensin RTD-1 using a bacterial expression system.Bioorganic & medicinal chemistry · 2018Article
- Rhesus θ-Defensin-1 Attenuates Endotoxin-induced Acute Lung Injury by Inhibiting Proinflammatory Cytokines and Neutrophil Recruitment.American journal of respiratory cell and molecular biology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
θ-Defensins are pleiotropic, macrocyclic peptides that are expressed uniquely in Old World monkeys. The peptides are potent, broad-spectrum microbicides that also modulate inflammatory responses in vitro and in animal models of viral infection and polymicrobial sepsis. θ-Defensins suppress proinflammatory cytokine secretion by leukocytes stimulated with diverse Toll-like receptor (TLR) ligands. Studies were performed to delineate anti-inflammatory mechanisms of rhesus θ-defensin 1 (RTD-1), the most abundant θ-defensin isoform in macaque granulocytes. RTD-1 reduced the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-8 in lipopolysaccharide (LPS)-stimulated human blood monocytes and THP-1 macrophages, and this was accompanied by inhibition of nuclear factor κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) pathways. Peptide inhibition of NF-κB activation occurred following stimulation of extracellular (TLRs 1/2 and 4) and intracellular (TLR9) receptors. Although RTD-1 did not inhibit MAPK in unstimulated cells, it induced phosphorylation of Akt in otherwise untreated monocytes and THP-1 cells. In the latter, this occurred within 10 min of RTD-1 treatment and produced a sustained elevation of phosphorylated Akt (pAkt) for at least 4 h. pAkt is a negative regulator of MAPK and NF-κB activation. RTD-1 inhibited IκBα degradation and p38 MAPK phosphorylation, and stimulated Akt phosphorylation in LPS-treated human primary monocytes and THP-1 macrophages. Specific inhibition of phosphatidylinositol 3-kinase (PI3K) blocked RTD-1-stimulated Akt phosphorylation and reversed the suppression of NF-κB activation by the peptide. These studies indicate that the anti-inflammatory properties of θ-defensins are mediated by activation of the PI3K/Akt pathway and suppression of proinflammatory signals in immune-stimulated cells.
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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.