LL-37

LL-37 is a cationic antimicrobial peptide with broad activity against bacteria, fungi, and viruses, and functions as an immune modulator that promotes wound healing and tissue regeneration.

- Support immune function and combat infections

- Promote wound healing and reduce inflammation

Mechanism of Action

How this peptide works in the body

Membrane Disruption:

LL-37 exerts its antimicrobial activity by interacting with negatively charged phospholipids on microbial membranes. This cationic peptide inserts itself into the lipid bilayer, forming transmembrane pores that compromise membrane integrity. The disruption of the electrochemical gradient leads to an influx of water and ions, causing osmotic lysis and subsequent microbial cell death. This mechanism is particularly effective against Gram-negative and Gram-positive bacteria, fungi, and some enveloped viruses.

Biofilm Inhibition:

LL-37 prevents the formation of bacterial biofilms by interfering with quorum sensing molecules, which regulate bacterial adhesion and communication. It disrupts key bacterial proteins, such as extracellular polymeric substances (EPS) and lipoteichoic acid (LTA), making it harder for bacteria to aggregate and establish biofilms. Additionally, LL-37 disperses pre-existing biofilms, increasing bacterial susceptibility to antibiotic treatment and host immune defenses.

Immunomodulation:

LL-37 modulates immune responses by binding to formyl peptide receptors (FPR2/ALX) on immune cells, including neutrophils, monocytes, and macrophages. This interaction enhances phagocytosis, promotes neutrophil chemotaxis, and regulates the activity of Toll-like receptors (TLRs). By influencing TLR2 and TLR4 signaling, LL-37 fine-tunes the balance between pro-inflammatory and anti-inflammatory cytokines, preventing excessive immune activation while enhancing microbial clearance.

Inflammatory Response Regulation:

LL-37 mitigates excessive inflammation by suppressing the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and interleukin-8 (IL-8). Simultaneously, it promotes the release of interleukin-10 (IL-10), an anti-inflammatory cytokine that helps resolve inflammation. Furthermore, LL-37 neutralizes lipopolysaccharides (LPS) from Gram-negative bacteria by directly binding to their lipid A moiety, reducing endotoxin-driven inflammation.

Tissue Regeneration:

LL-37 accelerates wound healing and tissue repair by stimulating keratinocyte proliferation and fibroblast migration. It upregulates vascular endothelial growth factor (VEGF), enhancing angiogenesis and improving blood supply to damaged tissues. Additionally, LL-37 activates matrix metalloproteinases (MMPs), which remodel the extracellular matrix and promote tissue regeneration, making it a promising therapeutic agent for chronic wounds, ulcers, and post-surgical recovery.