ArticlePloS one2012
Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- The macrocyclic peptide rhesus theta defensin 1 activates interferon and antiviral pathways in human monocytes.Journal of leukocyte biology · 2025Article
- Antimicrobial Peptides in Focus: Functional Potential and Translational Evidence from Swine Systems.ACS omega · 2025Review
- 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
- Resistance is futile: targeting multidrug-resistant bacteria withRSC chemical biology · 2023Review
- 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
- Emerging and future strategies in the management of recalcitrant Candida auris.Medical mycology · 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
- Antimicrobial Peptides and Their Applications in Biomedical Sector.Antibiotics (Basel, Switzerland) · 2021Review
- Anti-Inflammatory Effects of RTD-1 in a Murine Model of ChronicAntibiotics (Basel, Switzerland) · 2021Article
- Mechanism through Which Retrocyclin Targets Flavivirus Multiplication.Journal of virology · 2021Article
- Host Defense Peptides as Templates for Antifungal Drug Development.Journal of fungi (Basel, Switzerland) · 2020Review
- Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering.Frontiers in immunology · 2020Article
- RTD-1 therapeutically normalizes synovial gene signatures in rat autoimmune arthritis and suppresses proinflammatory mediators in RA synovial fibroblasts.Physiological genomics · 2019Article
- Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms.Scientific reports · 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
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Theta-defensins (θ-defensins) are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1-5 (RTDs 1-5). RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1-5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1-5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.
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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.