LL-37

preclinical

Also known as: Cathelicidin, hCAP-18

**Mechanism of Action** LL-37, the C-terminal active fragment of the human cathelicidin hCAP-18, exerts broad-spectrum antimicrobial activity primarily through membrane disruption via electrostatic interactions with negatively charged bacterial lipid bilayers, leading to pore formation and cell lysis. Beyond direct killing, LL-37 modulates innate immunity by chemoattracting immune cells (e.g., neutrophils, monocytes, T cells) via formyl peptide receptor-like 1 (FPRL1) and promoting cytokine release (e.g., IL-8, IL-6). It also enhances wound healing by stimulating keratinocyte migration, angiogenesis, and re-epithelialization through transactivation of epidermal growth factor receptor (EGFR) pathways. **Key Research Findings** Preclinical studies demonstrate LL-37’s efficacy against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains (e.g., MRSA, *P. aeruginosa*), as well as biofilm disruption. In murine wound models, topical LL-37 accelerates closure and reduces bacterial burden. However, its therapeutic potential is limited by susceptibility to proteolytic degradation and salt sensitivity in physiological conditions. Elevated LL-37 levels are linked to autoimmune conditions (e.g., psoriasis, rosacea), suggesting context-dependent dual roles in host defense and inflammation. **Clinical Relevance** Despite over 2,400 PubMed references, LL-37 remains in preclinical development. Challenges include optimizing stability (e.g., via peptide analogs or delivery systems) and mitigating pro-inflammatory effects in chronic inflammatory diseases. Its pleiotropic actions position it as a candidate for infected wounds, cystic fibrosis, and immunocompromised states, but no clinical trials have advanced to human efficacy studies. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Molecular weight
4493 g/mol
Molecular formula
C205H340N60O53
CAS number
154947-66-7
Administration
subcutaneous, topical
Research status
preclinical
References
2,508
Tags
antimicrobial, cathelicidin, innate-immunity

Research & studies

Human cathelicidin peptide LL-37 induces endothelial-to-mesenchymal transition
Bioscience, biotechnology, and biochemistry · 2025 · PubMed

LL-37 decreased endothelial cell markers and increased mesenchymal cell markers.; LL-37 reduced vascular network formation and increased cell migration.; LL-37-induced EndMT was inhibited by Akt and NF-κB inhibitors.; LL-37 may act as an EndMT inducer in atherosclerosis pathogenesis.

Significance of the LL-37 Peptide Delivered from Human Cathelicidin in the Pathogenesis, Treatment, and Diagnosis of Sepsis
Archivum immunologiae et therapiae experimentalis · 2025 · PubMed
Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease
Pharmacological research · 2024 · PubMed

LL-37 is an endogenous peptide with antimicrobial properties and multiple biological functions in heart disease.; LL-37 regulates atherosclerosis, thrombosis, inflammatory responses, and cardiac hypertrophy.; Engineered LL-37-related peptides have been developed and shown to regulate disease development.; The review clarifies LL-37's role in heart disease and provides direction for future research.

Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity
Biochemical and biophysical research communications · 2024 · PubMed

Vitamin D (50 nM) enhances CAMP mRNA levels ~170-fold in THP-1 cells.; hCAP18/LL-37 protein increases 3-4 times in cell lysates after vitamin D stimulation.; Proteasome inhibitor MG132 further elevates hCAP18/LL-37, indicating proteasomal degradation.; Synthetic LL-37 at 1.04 μM reduces MG63 osteoblast viability but less so for THP-1 cells.

Antifungal properties of cathelicidin LL-37: current knowledge and future research directions
World journal of microbiology & biotechnology · 2023 · PubMed
The LL-37 domain: A clue to cathelicidin immunomodulatory response?
Peptides · 2023 · PubMed
Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023 · PubMed

Cathelicidin LL-37 reduced intestinal injury and systemic inflammation in heat-stressed rats.; LL-37 improved multiple organ dysfunction, coagulopathy, and survival rate.; Protection was linked to preserving intestinal goblet cells and barrier function via increased transepithelial resistance, mucin-2, and Nrf2 expression.; High cathelicidin expression in ileal samples from inflammatory bowel disease patients correlated with better clinical outcomes.

Antibiofilm properties of cathelicidin LL-37: an in-depth review
World journal of microbiology & biotechnology · 2023 · PubMed

LL-37 prevents biofilm establishment in diverse pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli.; Key antibiofilm mechanisms include inhibition of bacterial adhesion, downregulation of biofilm-associated genes, and suppression of quorum-sensing pathways.; LL-37 degrades biofilm matrix and eradicates biofilm-residing cells.; In vivo efficacy and safety of LL-37 require further investigation.

Frequently asked questions

What is LL-37?

**Mechanism of Action** LL-37, the C-terminal active fragment of the human cathelicidin hCAP-18, exerts broad-spectrum antimicrobial activity primarily through membrane disruption via electrostatic interactions with negatively charged bacterial lipid bilayers, leading to pore formation and cell lysis. Beyond direct kil

How does LL-37 work?

Human cathelicidin antimicrobial peptide with broad-spectrum antibacterial, immunomodulatory, and wound-healing activity.

What is the research status of LL-37?

LL-37 is currently classified as preclinical, with 2,508 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of LL-37?

LL-37 has a molecular weight of approximately 4493 g/mol (formula C205H340N60O53).

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