Trial reportJournal of immunology (Baltimore, Md. : 1950)2014
Citrullination alters immunomodulatory function of LL-37 essential for prevention of endotoxin-induced sepsis.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Forensic application of CAMP expression for the determination of wound vitality in human compressed neck skin.International journal of legal medicine · 2026Article
- The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.Journal of internal medicine · 2026Review
- Host Defense Antimicrobial Peptides (HDPs) as Regulators of Hemostasis and Vascular Biology.Biomolecules · 2026Review
- LL-37 and citrullinated-LL-37 enhances oxylipins: citrullination attenuates LL-37-mediated COX-2-dependent chemokine response in human bronchial epithelial cells.Respiratory research · 2026Article
- Synergistic Alleviation of Inflammatory Cytokine Storms in Sepsis Rats by Low-Intensity Pulsed Ultrasound and Imipenem.Mediators of inflammation · 2026Article
- Citrullination of CAMP exacerbating mucosal inflammation in inflammatory bowel disease.Precision clinical medicine · 2025Article
- LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells.Journal of inflammation (London, England) · 2025Article
- Development and validation of a nomogram to predict bacterial blood stream infection.European journal of medical research · 2025Article
- Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates.Science advances · 2025Article
- Bidirectional Interaction Between Chronic Kidney Disease andJournal of immunology research · 2025Article
- The role of the mucosal barrier system in maintaining gut symbiosis to prevent intestinal inflammation.Seminars in immunopathology · 2024Review
- Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids.Biophysical journal · 2024Review
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Cathelicidin (LL-37) causes expression of inflammatory factors in coronary artery endothelial cells of Kawasaki disease by activating TLR4-NF-κB-NLRP3 signaling.Immunity, inflammation and disease · 2023Article
- Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?Inflammopharmacology · 2023Review
- Life satisfaction, generalized sense of self-efficacy and acceptance of illness in rheumatoid arthritis patients depending on age and severity of the disease.Reumatologia · 2023Article
- Antibacterial and Anti-Inflammatory Properties of a Novel Antimicrobial Peptide Derived from LL-37.Antibiotics (Basel, Switzerland) · 2022Article
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- Host and bacterial factors linking periodontitis and rheumatoid arthritis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Cathelicidin LL-37 plays an essential role in innate immunity by killing invading microorganisms and regulating the inflammatory response. These activities depend on the cationic character of the peptide, which is conferred by arginine and lysine residues. At inflammatory foci in vivo, LL-37 is exposed to peptidyl arginine deiminase (PAD), an enzyme released by inflammatory cells. Therefore, we hypothesized that PAD-mediated citrullination of the arginine residues within LL-37 will abrogate its immunomodulatory functions. We found that, when citrullinated, LL-37 was at least 40 times less efficient at neutralizing the proinflammatory activity of LPS due to a marked decrease in its affinity for endotoxin. Also, the ability of citrullinated LL-37 to quench macrophage responses to lipoteichoic acid and poly(I:C) signaling via TLR2 and TLR3, respectively, was significantly reduced. Furthermore, in stark contrast to native LL-37, the modified peptide completely lost the ability to prevent morbidity and mortality in a mouse model of d-galactosamine-sensitized endotoxin shock. In fact, administration of citrullinated LL-37 plus endotoxin actually exacerbated sepsis due to the inability of LL-37 to neutralize LPS and the subsequent enhancement of systemic inflammation due to increased serum levels of IL-6. Importantly, serum from septic mice showed increased PAD activity, which strongly correlated with the level of citrullination, indicating that PAD-driven protein modification occurs in vivo. Because LL-37 is a potential treatment for sepsis, its administration should be preceded by a careful analysis to ensure that the citrullinated peptide is not generated in treated patients.
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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.