LL-37

LL-37 (Cathelicidin Antimicrobial Peptide): Molecular Mechanism and Immunological Function

Molecular Overview

LL-37, also known as human cathelicidin antimicrobial peptide (hCAP-18/LL-37), is an endogenous cationic α-helical peptide derived from the C-terminal cleavage of the cathelicidin precursor hCAP-18 by proteinase 3 in neutrophil granules.

It constitutes a critical component of the innate immune system, serving as a first-line effector molecule in host defense against a broad spectrum of bacterial, viral, and fungal pathogens.

Its amphipathic structure allows LL-37 to integrate into and disrupt microbial membranes via electrostatic interactions with negatively charged phospholipids, leading to membrane permeabilization and microbial lysis.

Mechanism of Action

• Direct Antimicrobial Activity
  LL-37 exerts broad-spectrum microbicidal effects through membrane disruption, pore formation, and metabolic interference. It binds to bacterial lipopolysaccharides (LPS) and lipoteichoic acids, neutralizing endotoxin activity and reducing pathogen-induced inflammation.
   
• Biofilm Disruption
  By interfering with extracellular polymeric substances (EPS) and quorum-sensing signals, LL-37 destabilizes bacterial biofilms, improving susceptibility to immune clearance and antibiotic penetration
   
• Immunomodulatory Function
  Beyond its antimicrobial action, LL-37 acts as an immune signaling peptide.
  
  It activates formyl peptide receptor-like 1 (FPR2) and P2X7 receptors on macrophages, neutrophils, and keratinocytes, modulating cytokine production, chemotaxis, and angiogenesis.
  
  This dual antimicrobial and immunomodulatory role bridges innate and adaptive immunity.
   
• Wound Healing and Tissue Regeneration
  LL-37 promotes re-epithelialization, keratinocyte migration, and fibroblast proliferation via EGFR transactivation and VEGF upregulation, leading to enhanced angiogenesis and tissue repair in dermal and mucosal injury models.
   
• Inflammation Regulation
  At physiological concentrations, LL-37 suppresses excessive pro-inflammatory signaling by inhibiting TLR4–NF-κB activation while concurrently upregulating IL-10 and other anti-inflammatory mediators. This balance prevents chronic inflammation and supports immune homeostasis.

Physiological and Clinical Effects

• Antimicrobial Defense: Potent activity against Gram-positive and Gram-negative bacteria, enveloped viruses, and fungal pathogens.
• Biofilm Degradation: Disrupts microbial biofilms resistant to conventional antibiotics.
• Accelerated Wound Healing: Stimulates cell migration, angiogenesis, and extracellular matrix remodeling.
• Immune System Support: Enhances innate immune recognition and promotes barrier integrity in epithelial tissues.
• Inflammation Modulation: Reduces inflammatory cytokine burden while maintaining pathogen clearance efficiency.

Therapeutic and Research Applications

LL-37 is being investigated for its therapeutic potential in:

• Chronic and resistant infections (bacterial, viral, and fungal)
• Wound healing disorders and post-surgical recovery
• Inflammatory and autoimmune conditions such as psoriasis and ulcerative colitis
• Biofilm-associated infections and antimicrobial resistance models

As a host-defense peptide (HDP), LL-37 represents a promising multi-functional immunotherapeutic candidate, combining direct antimicrobial efficacy, immune modulation, and tissue regenerative properties within a single molecular framework.

Legal Policy: 

This product is strictly for research purposes only and is intended solely for in vitro testing and laboratory experimentation. The information provided on this website is for educational use and does not permit the introduction of this product into humans or animals. Handling of this product is restricted to licensed and qualified professionals. It is not classified as a drug, food, or cosmetic, and should not be misrepresented or used as such.

All products sold on this site are for research and development use only. They are not intended for human or animal use.

The statements on this website have not been evaluated by the US Food and Drug Administration (FDA). Our products and content are not intended to diagnose, treat, cure, or prevent any disease.

Tides Peptides is a chemical supplier, not a compounding pharmacy or a chemical compounding facility as defined under section 503A of the Federal Food, Drug, and Cosmetic Act.

Molecular Formula

• Sequence: -Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-GIn-Arg-lle-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser
• Formula: C₂₀₅H₃₄₀N₆O₅₃
• Molecular Weight: ~4493.342 g/mol

View Certificate of Analysis

1. What is LL-37, and why does it matter?
LL-37 is a naturally occurring antimicrobial peptide that plays a key role in the body’s immune defense. It matters because it helps fight infections, reduce inflammation, and promote wound healing.

2. What are the benefits of LL-37?
People use LL-37 for:

• Antiviral, antibacterial, and antifungal protection
• Enhanced wound healing and tissue repair
• Immune system support
• Reduction of inflammation

3. What is LL-37 used for?
LL-37 is used to support the immune system, treat chronic infections, promote healing of wounds, and as a potential therapy for inflammatory and autoimmune conditions.

Antimicrobial Peptide, LL-37, And Its Potential As An Anti-HIV Agent.
Vera-Cruz A, Tanphaichitr N, Angel JB.Clin Invest Med. 2021 Oct 3;44(3):E64-71. doi: 10.25011/cim.v44i3.36657.PMID: 34600462 Review.

Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease.
Miao S, Liu H, Yang Q, Zhang Y, Chen T, Chen S, Mao X, Zhang Q.Pharmacol Res. 2024 Dec;210:107529. doi: 10.1016/j.phrs.2024.107529. Epub 2024 Nov 28.PMID: 39615616 Review.

LL-37, the master antimicrobial peptide, its multifaceted role from combating infections to cancer immunity.
Keshri AK, Rawat SS, Chaudhary A, Sharma S, Kapoor A, Mehra P, Kaur R, Mishra A, Prasad A.Int J Antimicrob Agents. 2025 Jan;65(1):107398. doi: 10.1016/j.ijantimicag.2024.107398. Epub 2024 Dec 4.PMID: 39643165 Review.

Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression.
Chen X, Deng S, Wang W, Castiglione S, Duan Z, Luo L, Cianci F, Zhang X, Xu J, Li H, Zhao J, Kamau PM, Zhang Z, Mwangi J, Li J, Shu Y, Hu X, Mazzanti M, Lai R.Mol Psychiatry. 2022 Nov;27(11):4790-4799. doi: 10.1038/s41380-022-01790-6. Epub 2022 Sep 22.PMID: 36138130

LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity.
Wei X, Zhang L, Yang Y, Hou Y, Xu Y, Wang Z, Su H, Han F, Han J, Liu P, Hu S, Koci MD, Sun X, Zhang C.Cell Rep. 2022 May 31;39(9):110880. doi: 10.1016/j.celrep.2022.110880.PMID: 35649354
 

Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.
Svensson D, Nilsson BO.Inflamm Res. 2025 Feb 11;74(1):36. doi: 10.1007/s00011-025-02005-8.PMID: 40063262 Free PMC article. Review.

The potentials of short fragments of human anti-microbial peptide LL-37 as a novel therapeutic modality for diseases.
Chen K, Gong W, Huang J, Yoshimura T, Wang JM.Front Biosci (Landmark Ed). 2021 Nov 30;26(11):1362-1372. doi: 10.52586/5029.PMID: 34856773 Review.

Rosacea: Pathogenesis and Therapeutic Correlates.
Geng RSQ, Bourkas AN, Mufti A, Sibbald RG.J Cutan Med Surg. 2024 Mar-Apr;28(2):178-189. doi: 10.1177/12034754241229365. Epub 2024 Mar 7.PMID: 38450615 Free PMC article. Review.
 

LL-37_Renalexin hybrid peptide exhibits antimicrobial activity at lower MICs than its counterpart single peptides.
Narh JK, Casillas-Vega NG, Zarate X.Appl Microbiol Biotechnol. 2024 Dec;108(1):126. doi: 10.1007/s00253-023-12887-5. Epub 2024 Jan 13.PMID: 38229302 Free PMC article.

Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke.
Shih CC, Liao WC, Ke HY, Kuo CW, Tsao CM, Tsai WC, Chiu YL, Huang HC, Wu CC.Biomed Pharmacother. 2023 May;161:114565. doi: 10.1016/j.biopha.2023.114565. Epub 2023 Mar 21.PMID: 36958193