ArticleFrontiers in immunology2018
Host Defense Peptide LL-37-Mediated Chemoattractant Properties, but Not Anti-Inflammatory Cytokine IL-1RA Production, Is Selectively Controlled by Cdc42 Rho GTPase
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Resistance mechanisms of bacterial biofilms on orthopedic implants and research progress on novel anti-biofilm coatings.Frontiers in bioengineering and biotechnology · 2026Review
- 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
- Rho-GTPases subfamily: cellular defectors orchestrating viral infection.Cellular & molecular biology letters · 2025Review
- Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Suramin blocked hCAP18/LL-37-induced macrophage recruitment and M2 polarization to enhance the therapeutic efficacy of 1,25(OH)Frontiers in nutrition · 2025Article
- Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Porcine β-Defensin 114: Creating a Dichotomous Response to Inflammation.International journal of molecular sciences · 2024Article
- Immunomodulatory peptides: new therapeutic horizons for emerging and re-emerging infectious diseases.Frontiers in microbiology · 2024Review
- Article
- Macrophages immunomodulation induced by Porphyromonas gingivalis and oral antimicrobial peptides.Odontology · 2023Review
- Article
- Understanding the Roles of Host Defense Peptides in Immune Modulation: From Antimicrobial Action to Potential as Adjuvants.Journal of microbiology and biotechnology · 2023Review
- Combination of IL-17A/F and TNF-α uniquely alters the bronchial epithelial cell proteome to enhance proteins that augment neutrophil migration.Journal of inflammation (London, England) · 2022Article
- Cell division control 42 elevates during infliximab therapy, and its increment relates to treatment response in ulcerative colitis patients.Journal of clinical laboratory analysis · 2022Article
- Host Defence Peptides: A Potent Alternative to Combat Antimicrobial Resistance in the Era of the COVID-19 Pandemic.Antibiotics (Basel, Switzerland) · 2022Review
- Host Defense Peptides LL-37 and Lactoferrin Trigger ET Release from Blood-Derived Circulating Monocytes.Biomedicines · 2022Article
- Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)Cell death discovery · 2022Article
- Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging.Frontiers in cellular neuroscience · 2022Review
- Are Host Defense Peptides and Their Derivatives Ready to be Part of the Treatment of the Next Coronavirus Pandemic?Archivum immunologiae et therapiae experimentalis · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The human host defense peptide LL-37 promotes immune activation such as induction of chemokine production and recruitment of leukocytes. Conversely, LL-37 also mediates anti-inflammatory responses such as production of anti-inflammatory cytokines, e.g., IL-1RA, and the control of pro-inflammatory cytokines, e.g., TNF. The mechanisms regulating these disparate immunomodulatory functions of LL-37 are not completely understood. Rho GTPases are GTP-binding proteins that promote fundamental immune functions such as chemokine production and recruitment of leukocytes. However, recent studies have shown that distinct Rho proteins can both negatively and positively regulate inflammation. Therefore, we interrogated the role of Rho GTPases in LL-37-mediated immunomodulation. We demonstrate that LL-37-induced production of chemokines, e.g., GRO-α and IL-8 is largely dependent on Cdc42/Rac1 Rho GTPase, but independent of the Ras pathway. In contrast, LL-37-induced production of the anti-inflammatory cytokine IL-1RA is not dependent on either Cdc42/Rac1 RhoGTPase or Ras GTPase. Functional studies confirmed that LL-37-induced recruitment of leukocytes (monocytes and neutrophils) is also dependent on Cdc42/Rac1 RhoGTPase activity. We demonstrate that Cdc42/Rac1-dependent bioactivity of LL-37 involves G-protein-coupled receptors (GPCR) and JNK mitogen-activated protein kinase (MAPK) signaling, but not p38 or ERK MAPK signaling. We further show that LL-37 specifically enhances the activity of Cdc42 Rho GTPase, and that the knockdown of Cdc42 suppresses LL-37-induced production of chemokines without altering the peptide's ability to induce IL-1RA. This is the first study to demonstrate the role of Rho GTPases in LL-37-mediated responses. We demonstrate that LL-37 facilitates chemokine production and leukocyte recruitment engaging Cdc42/Rac1 Rho GTPase
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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.