ll-37
A cytomed‑originated peptide complex often discussed in the context of cellular regulation.
Key Research Properties:
| SKU: | ll-37 |
|---|---|
| Purity: | >99% (HPLC Verified) |
| Form: | Lyophilized Powder |
| Storage: | Store at -20°C |
| CAS Number: | 195875-84-4 |
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What is LL-37?
LL-37 is the sole human cathelicidin peptide, generated when the hCAP18 precursor is proteolytically processed into a 37–amino acid, cationic α-helix that binds microbial membranes and tunes innate immune responses[1], [2]. Because it simultaneously kills pathogens, coordinates chemotaxis, and supports tissue repair, LL-37 has become a central biomarker and experimental therapeutic in mucosal immunity, dermatology, and infectious disease research[3], [5].
Molecular Fingerprint
- Precursor: hCAP18 (
CAMPgene) stored in neutrophil granules and epithelial secretory vesicles[1] - Sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES with net charge +6 at physiological pH[1]
- Processing: Proteinase 3, kallikreins, and other serine proteases liberate active LL-37 from hCAP18[4]
- Structure: Amphipathic α-helix that dimerises on lipid bilayers and nucleic acids[1], [4]
- Baseline Sources: Neutrophils, airway and gut epithelia, keratinocytes, salivary glands, sweat[2], [3]
Functional Portfolio
- Broad-spectrum antimicrobial: Rapidly perforates bacterial and fungal membranes at micromolar concentrations[1], [6]
- Immune choreography: Engages FPR2, P2X7, and EGFR to drive chemotaxis, cytokine tuning, and barrier repair[2], [4]
- Wound and angiogenic support: Stimulates keratinocyte migration, fibroblast proliferation, and endothelial sprouting[5]
- Oncology signal: Aberrant LL-37 contributes to tumor immune evasion or suppression in a context-dependent manner[5]
- Antiviral defense: Blocks viral fusion and enhances interferon pathways in respiratory and mucosal infections[7], [10]
Peptide Illustration
LL-37 structural artwork, Vital Healer graphics archive.
| Property | Value |
|---|---|
| CAS Number | 195875-84-4 |
| Length | 37 amino acids (residues 134-170 of hCAP18) |
| Molecular Weight | ≈ 4.49 kDa[1] |
| Net Charge / pI | +6 at neutral pH; isoelectric point ≈ 11.0[1] |
| Precursor Gene | CAMP (chromosome 3p21.31)[2] |
| Primary Processing Enzymes | Neutrophil proteinase 3; epidermal kallikrein 5 and 7[4] |
Vitamin D axis
1,25(OH)2D regulates CAMP transcription via VDRE motifs, linking sunlight and supplementation to LL-37 availability[3].
Mechanism of Action
LL-37 operates through a dual-action model: rapid membrane disruption that eliminates microbes, and receptor-driven signalling that recalibrates innate and adaptive responses[1], [2].
Direct Antimicrobial Killing
- Carpet & toroidal pore formation: The amphipathic helix decorates microbial membranes, collapses membrane potential, and causes leakage at 1–10 µM concentrations[1].
- Biofilm disruption: LL-37 penetrates extracellular polymeric matrices, interferes with quorum sensing, and sensitises biofilm bacteria to antibiotics[6].
- Viral envelope destabilisation: The peptide binds viral glycoproteins and prevents fusion, complementing its ability to enhance interferon responses[10].
Host Signalling & Immune Modulation
- Pattern-recognition tuning: LL-37 neutralises LPS/LTA and suppresses excessive TLR4 signalling while still permitting pathogen clearance[2], [3].
- Receptor activation: Engagement of FPR2, P2X7, EGFR, and IGF1R triggers chemotaxis, cytokine release, autophagy, and epithelial restitution[2], [4].
- Immune cell recruitment: LL-37 gradients recruit neutrophils, monocytes, mast cells, and T cells to sites of injury, linking innate and adaptive immunity[3].
Tissue Repair & Resolution
- Keratinocyte and fibroblast activation: LL-37 transactivates EGFR to accelerate migration and proliferation during re-epithelialisation[5].
- Angiogenesis: It induces VEGF and stimulates endothelial tube formation, improving perfusion in ischemic tissue[5].
- Autoimmune balance: Dysregulated LL-37–DNA complexes can aberrantly trigger plasmacytoid dendritic cells, linking the peptide to lupus and psoriasis pathogenesis[7].
Research & Evidence
Broad-Spectrum Antimicrobial Activity
Planktonic Pathogens
LL-37 disrupts bacterial and fungal membranes within micromolar ranges, producing rapid loss of membrane potential and cell death[8].
- Kills Gram-positive and Gram-negative bacteria, including Pseudomonas and Staphylococcus
- Exerts fungicidal effects against Candida species
- Displays virucidal activity against enveloped viruses
Biofilm Disruption
LL-37 penetrates and destabilises bacterial biofilms, reducing biomass and sensitising communities to antibiotics[9].
- Prevents biofilm establishment on abiotic surfaces
- Down-regulates quorum sensing pathways
- Acts synergistically with conventional antibiotics
Immune Modulation & Vitamin D Axis
Innate Immune Signalling
LL-37 modulates Toll-like receptor signalling, chemotaxis, and cytokine production, acting as a multifunctional host-defence peptide[7], [12].
- Neutralises LPS/LTA to prevent excessive TLR4 activation
- Engages FPR2/P2X7 receptors to guide leukocyte recruitment
- Shapes dendritic cell and macrophage differentiation
Vitamin D-Induced Expression
Active vitamin D (1,25(OH)2D3) directly induces CAMP gene transcription, linking nutritional status to LL-37 output and innate immunity[4].
- Vitamin D receptor binding to CAMP promoter elevates LL-37 mRNA
- Supplementation studies show increased circulating LL-37
- Explains epidemiologic links between vitamin D deficiency and infection risk
Tissue Repair & Barrier Homeostasis
Wound Healing
LL-37 accelerates re-epithelialisation, enhances keratinocyte migration, and promotes angiogenesis in cutaneous wounds[5], [11].
- Topical LL-37 improves closure of chronic ulcers and burn models
- Regulates growth factors (EGFR, VEGF) critical for tissue repair
- Serves as biomarker for non-healing wounds
Barrier & Disease Contexts
Aberrant LL-37 expression contributes to inflammatory skin disorders (rosacea, psoriasis) and displays context-dependent roles in cancer biology[6], [10].
- Excess proteolytic processing drives rosacea inflammation
- LL-37–nucleic acid complexes can activate autoimmune pathways
- Tumour microenvironment dictates pro- vs. anti-tumour LL-37 effects
Dosing & Administration
Effective LL-37 concentrations depend on the experimental model, ranging from micromolar antimicrobial assays to topical formulations evaluated in animal and human studies[8]-[11], [13], [14].
Clinical Trial Dosing (Human Research)
Clinical trial protocols:
- Intratumoral melanoma study (NCT02225366): Weekly injections into 2–4 lesions for eight weeks across escalating dose cohorts[13]
- Diabetic foot ulcer study (NCT04098562): 0.5 mg/mL LL-37 cream applied twice weekly for four weeks alongside standard wound care[14]
Use these published regimens as reference points when designing translational research or formulation studies.
Storage & Handling
Storage Conditions
- Lyophilized powder: -20°C or -80°C
- Reconstituted solution: Store at -20°C; avoid repeated freeze-thaw
- Working aliquots: Store at 4°C for up to 1 week
- Light-sensitive: Store in amber vials or wrapped in foil
Reconstitution
- Solvent: Sterile water, PBS, or acetic acid (0.01% for long-term storage)
- Concentration: Prepare 1 mg/mL stock solution
- Method: Gently dissolve; avoid vigorous vortexing
- Aliquoting: Prepare single-use aliquots to minimize freeze-thaw cycles
Stability Notes
- LL-37 is relatively stable in solution at pH 5-7
- Susceptible to proteolytic degradation in serum
- Add protease inhibitors for cell culture studies with serum
- Verify purity by HPLC/mass spec after prolonged storage
Safety & Side Effects
Published clinical protocols and preclinical studies report favourable safety profiles for LL-37 in controlled topical and intratumoral applications[8], [10], [13], [14].
Clinical Safety Data
Safety Profile from Human Clinical Trials
Registry takeaways:
- Topical LL-37 (NCT04098562): Study design emphasises local tolerability; no LL-37–attributed serious adverse events reported in the registry synopsis[14].
- Intratumoral LL-37 (NCT02225366): Weekly dosing guided by CTCAE monitoring; registry description notes dose-escalation without predefined systemic toxicity signals[13].
- Systemic exposure: Preclinical pharmacokinetic studies suggest minimal systemic uptake following topical delivery, consistent with clinical observations[10].
Preclinical Safety Considerations
Preclinical Observations
Potential Risks & Contraindications
Theoretical Concerns (Limited Clinical Data):
Autoimmune Exacerbation:
LL-37–nucleic acid complexes activate plasmacytoid dendritic cells; model autoimmune settings (psoriasis, lupus) with caution[6].
Cancer Considerations:
LL-37 can either inhibit or support tumour growth depending on microenvironmental cues; incorporate rigorous controls in oncologic studies[10].
Excessive Inflammation:
High concentrations may amplify pro-inflammatory signalling; titrate doses to balance antimicrobial and immunomodulatory effects[7], [12].
Hypersensitivity:
Peptide-based agents can elicit allergic responses in sensitised subjects; monitor for hypersensitivity during exploratory dosing.
Laboratory Safety
Standard Laboratory Precautions:
- Wear appropriate PPE (gloves, lab coat, safety glasses)
- Avoid generating aerosols during handling
- Work in biosafety cabinet when handling concentrated solutions
- Dispose of according to institutional biosafety guidelines
- No special biohazard classification for purified peptide
Frequently Asked Questions
CAMP promoter. Binding of 1,25-dihydroxyvitamin D₃ to the vitamin D receptor induces LL-37 transcription, linking nutritional status to antimicrobial readiness[4].
Clinical Trials & Human Evidence Landscape
Recent LL-37 studies range from interventional oncology and wound-healing trials to observational biomarker investigations in oral and periodontal disease. Registered trials with publicly available protocols are summarised below.
Interventional Studies
Intratumoral LL-37 for Melanoma (NCT02225366)
- Sponsor / Site: MD Anderson Cancer Center, USA[13]
- Design: Phase I dose-escalation with weekly intratumoral LL-37 for eight weeks; 2 participants per cohort, up to four dose levels (planned n=36).
- Population: Adults with injectable melanoma lesions refractory to standard therapy.
- Primary Endpoint: Optimal Biological Dose based on CTCAE dose-limiting toxicities.
- Secondary Endpoints: Immune-related response (irCR/irPR), T-cell phenotyping, radiologic response every 8 weeks.
- Status: Completed; results pending peer-reviewed publication.
Topical LL-37 Cream for Diabetic Foot Ulcers (NCT04098562)
- Sponsor: Universitas Indonesia[14]
- Design: Randomised, placebo-controlled pilot (n=40) delivering 0.5 mg/mL LL-37 cream plus standard wound care twice weekly for four weeks.
- Primary Outcomes: Granulation index (ImageJ) and qualitative aerobic bacterial culture at weeks 1–4.
- Secondary Outcomes: Wound area reduction, cytokine profiling (IL‑1α, TNF‑α).
- Status: Not yet recruiting (last verified September 2019).
Periodontal & Oral Health Studies
Vitamin D & LL-37 Around Implants (NCT06867250)
- Sponsor: Altınbaş University, Türkiye[15]
- Design: Cross-sectional analysis of 33 patients (105 implants) spanning peri-implant health, mucositis, and peri-implantitis.
- Assessments: Clinical indices (mPI, mSBI, probing depth, keratinised mucosa width) and peri-implant sulcus fluid LL-37/vitamin D via ELISA.
- Status: Completed December 2021; statistical analysis underway.
Passive Smoking & Salivary LL-37 in Children (NCT03639376)
- Sponsor: Kırıkkale University, Türkiye[16]
- Design: Observational cohort of 180 children (90 exposed vs. 90 unexposed household smoke).
- Primary Measure: Salivary LL-37 concentration across an 18-month sampling window.
- Secondary Measure: Salivary cotinine to validate passive smoke exposure.
- Status: Completed (2018); awaiting disseminated results.
Smoking, Vitamin D₃ & Periodontal LL-37 (NCT03923218)
- Sponsor: Gazi University, Türkiye[17]
- Design: Case-control (n=60) comparing smokers with chronic periodontitis, non-smokers with periodontitis, and healthy controls.
- Endpoints: Gingival crevicular fluid LL-37 (ELISA), serum vitamin D₃ (HPLC), periodontal parameters (PD, CAL, GI, PI).
- Status: Completed; manuscript in preparation.
LL-37 in Oral Potentially Malignant Lesions (NCT06219330)
- Sponsor: Fayoum University, Egypt[18]
- Design: Case-control (n=45) including healthy subjects, oral lichen planus, and leukoplakia.
- Primary Outcomes: Salivary LL-37 levels, ROC characteristics for lesion discrimination.
- Status: Completed November 2023; results posted January 2024.
Additional Registered Studies
- Skin Barrier & Surfactants (NCT01951352): Interventional crossover (n=10) tracking LL-37 expression after washing with different soaps using tape-stripping timepoints at 5 min, 4 h, and 24 h[19].
- Periodontal Therapy Biomarkers (NCT04404335): Prospective study relating LL-37, IL-10, and TGF-β changes to periodontal treatment response[20].
- Passive Smoking, Oxidative Stress & LL-37 (NCT04292548): Observational study connecting salivary LL-37 and oxidative indices with pediatric passive smoking exposure[21].
References & Scientific Citations
The information provided on this page is supported by peer-reviewed scientific research. Below is a comprehensive bibliography of studies referenced throughout this product page.
Research Integrity:
All claims made on this page are backed by published scientific literature. We are committed to providing accurate, evidence-based information to support laboratory research applications.
- Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39-48. PMID: 12960280
- Dürr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta. 2006;1758(9):1408-1425. PMID: 16716248
- Agerberth B, et al. The human antimicrobial and chemotactic peptides LL-37 and α-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96(9):3086-3093. PMID: 11049988
- Wang TT, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909-2912. PMID: 15322146
- Schauber J, Gallo RL. Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol. 2008;122(2):261-266. PMID: 18439663
- Yamasaki K, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975-980. PMID: 17676051
- Mookherjee N, Hancock REW. Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci. 2007;64(7-8):922-933. PMID: 17310278
- Turner J, et al. Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother. 1998;42(9):2206-2214. PMID: 9736536
- Overhage J, et al. Human host defence peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76(9):4176-4182. PMID: 18591225
- Vandamme D, Landuyt B, Luyten W, Schoofs L. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol. 2012;280(1):22-35. PMID: 23246832
- Heilborn JD, et al. The cathelicidin antimicrobial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120(3):379-389. PMID: 12603850
- van der Does AM, et al. The human cathelicidin LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 2010;185(10):7084-7093. PMID: 20952669
- ClinicalTrials.gov. Intratumoral Injections of LL37 for Melanoma. Identifier: NCT02225366. Updated December 9, 2021. https://clinicaltrials.gov/study/NCT02225366
- ClinicalTrials.gov. The Efficacy of LL-37 Cream on Aerobic Bacteria Colonization Pattern, Inflammation Response, and Healing Rate of Diabetic Foot Ulcers. Identifier: NCT04098562. Verified September 2019. https://clinicaltrials.gov/study/NCT04098562
- ClinicalTrials.gov. Peri-implant Vitamin D and Cathelicidin (LL-37) Levels. Identifier: NCT06867250. Updated March 10, 2025. https://clinicaltrials.gov/study/NCT06867250
- ClinicalTrials.gov. Passive Smoking and LL-37 in Children. Identifier: NCT03639376. Updated August 21, 2018. https://clinicaltrials.gov/study/NCT03639376
- ClinicalTrials.gov. Effects of Smoking and Vitamin D3 on the Levels of Human Cathelicidin Peptide LL-37. Identifier: NCT03923218. Updated April 22, 2019. https://clinicaltrials.gov/study/NCT03923218
- ClinicalTrials.gov. Cathelicidin LL-37 Relation to Potentially Malignant Lesions. Identifier: NCT06219330. Updated January 23, 2024. https://clinicaltrials.gov/study/NCT06219330
- ClinicalTrials.gov. Effects of Surfactants on the Innate Immune System. Identifier: NCT01951352. Updated October 2, 2019. https://clinicaltrials.gov/study/NCT01951352
- ClinicalTrials.gov. The Role of Anti-inflammatory Cytokines and Antimicrobial Peptide LL-37 Biomarkers in the Treatment of Periodontal Disease. Identifier: NCT04404335. Updated September 30, 2022. https://clinicaltrials.gov/study/NCT04404335
- ClinicalTrials.gov. Salivary TAS, TOS, LL-37 and Dental Status in Passive Smoking Children. Identifier: NCT04292548. Updated March 6, 2020. https://clinicaltrials.gov/study/NCT04292548
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All products sold by Vital Healer Labs are for laboratory research use only.
Not for human consumption, medical, or veterinary use.