ArticleAmerican journal of respiratory cell and molecular biology2018
Rhesus θ-Defensin-1 Attenuates Endotoxin-induced Acute Lung Injury by Inhibiting Proinflammatory Cytokines and Neutrophil Recruitment.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Daily Intake of Fermented Milk ContainingNutrients · 2019Trial
- Extracellular vesicle-mediated mechanisms and therapeutic potential in acute lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Progression of Acute Lung Injury in Intratracheal LPS Rat Model: Efficacy of Fluticasone, Dexamethasone, and Pirfenidone.Pharmacology · 2024Article
- 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
- LTB4 Promotes Acute Lung Injury via Upregulating the PLCDisease markers · 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
- Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids.Human genomics · 2021Article
- Host Defense Peptides as Templates for Antifungal Drug Development.Journal of fungi (Basel, Switzerland) · 2020Review
- 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
- Update in Critical Care and Acute Respiratory Distress Syndrome 2018.American journal of respiratory and critical care medicine · 2019Article
- PP2ACα of Alveolar Macrophages Is a Novel Protective Factor for LPS-Induced Acute Respiratory Distress Syndrome.Inflammation · 2019Article
- Macrocyclic θ-defensins suppress tumor necrosis factor-α (TNF-α) shedding by inhibition of TNF-α-converting enzyme.The Journal of biological chemistry · 2018Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Acute lung injury (ALI) is a clinical syndrome characterized by acute respiratory failure and is associated with substantial morbidity and mortality. Rhesus θ-defensin (RTD)-1 is an antimicrobial peptide with immunomodulatory activity. As airway inflammation and neutrophil recruitment and activation are hallmarks of ALI, we evaluated the therapeutic efficacy of RTD-1 in preclinical models of the disease. We investigated the effect of RTD-1 on neutrophil chemotaxis and macrophage-driven pulmonary inflammation with human peripheral neutrophils and LPS-stimulated murine alveolar macrophage (denoted MH-S) cells. Treatment and prophylactic single escalating doses were administered subcutaneously in a well-established murine model of direct endotoxin-induced ALI. We assessed lung injury by histopathology, pulmonary edema, inflammatory cell recruitment, and inflammatory cytokines/chemokines in the BAL fluid. In vitro studies demonstrated that RTD-1 suppressed CXCL8-induced neutrophil chemotaxis, TNF-mediated neutrophil-endothelial cell adhesion, and proinflammatory cytokine release in activated murine alveolar immortalized macrophages (MH-S) cells. Treatment with RTD-1 significantly inhibited in vivo LPS-induced ALI by reducing pulmonary edema and histopathological changes. Treatment was associated with dose- and time-dependent inhibition of proinflammatory cytokines (TNF, IL-1β, and IL-6), peroxidase activity, and neutrophil recruitment into the airways. Antiinflammatory effects were demonstrated in animals receiving RTD-1 up to 12 hours after LPS challenge. Notably, subcutaneously administered RTD-1 demonstrates good peptide stability as demonstrated by the long in vivo half-life. Taken together, these studies demonstrate that RTD-1 is efficacious in an experimental model of ALI through inhibition of neutrophil chemotaxis and adhesion, and the attenuation of proinflammatory cytokines and gene expression from alveolar macrophages.
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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.