Description

LL-37 – Technical Biochemical Mechanism Profile

(Cationic Antimicrobial Host-Defense Peptide; Cathelicidin-Derived – Research Use Only)

LL-37 is a 37-amino-acid cationic α-helical peptide derived from the C-terminal cleavage of the human cathelicidin precursor hCAP-18.
In vitro models demonstrate that LL-37 exerts broad-spectrum antimicrobial, immunomodulatory, and wound-repair signaling functions through membrane disruption, TLR signaling modulation, and EGFR/MAPK pathway activation, resulting in differential gene transcription across immune and epithelial systems.

---

✅ 1. Molecular and Cellular Targets

LL-37 interacts with:

• Bacterial and viral membranes (negatively charged phospholipids → pore formation)

• TLR2, TLR4, TLR9 (pattern-recognition receptors)

• P2X7 purinergic receptor

• EGFR (epidermal growth factor receptor)

• FPR2 (formyl peptide receptor-2) on immune and epithelial cells

These interactions trigger downstream cytokine, chemokine, and repair-related signaling cascades.

---

✅ 2. Core Biochemical Mechanisms

A. Membrane Disruption (Pathogen-Directed)

• Electrostatic binding to anionic phospholipids

• α-helix insertion into lipid bilayers

• Pore formation → membrane lysis

• Loss of ionic gradient and metabolic collapse in microbes

---

B. Immunomodulatory Signaling (Host-Directed)

TLR Modulation

LL-37 directly binds:

• TLR2/TLR4 ligands → altered NF-κB output

• CpG-DNA → TLR9 signaling

• Inhibits LPS–TLR4 inflammatory amplification

NF-κB Downstream Targets Affected:

• ↓ TNFA, IL1B, IL6, COX-2 (PTGS2)

• ↑ IL10, TGFB1

---

P2X7 Pathway

Binding to P2X7 receptors promotes:

• ↑ Ca²⁺ influx

• NLRP3 inflammasome activation in some immune cell types

• IL-1β maturation and release

---

C. EGFR / MAPK / ERK Signaling (Tissue Models)

LL-37 triggers transactivation of EGFR, producing:

• ↑ ERK1/2 phosphorylation

• ↑ MAPK activation

• ↑ CREB-regulated transcription

Genes commonly monitored:

• VEGFA (angiogenesis)

• EGF, FGF2

• MMP9, MMP2 (matrix remodeling)

• COL1A1, FN1 (extracellular matrix organization)

---

D. Chemotactic Signaling via FPR2

LL-37 functions as a ligand for FPR2/ALX:

• Activation of G-protein–dependent Ca²⁺ flux

• Neutrophil and macrophage chemotaxis

• Recruitment of immune cells to injury or infection sites in research models

---

✅ 3. Enzymes & Second Messengers

---

✅ 4. Gene Targets Frequently Measured in Research

---

✅ 5. Antimicrobial Actions

• Cationic amphipathic helix binds microbial envelopes

• Inserts into membrane → torroidal pore formation

• Leads to ion leakage, ATP loss, membrane rupture

Targets include:

• Gram-positive & Gram-negative bacteria

• Fungi

• Enveloped viruses (via membrane interaction)

---

✅ Mechanistic Summary

• Endogenous human cathelicidin-derived peptide

• Broad GPCR, TLR, and EGFR signaling effects

• Activates MAPK/ERK, NF-κB modulation, P2X7–Ca²⁺ influx, and MMP/VEGF gene pathways

• Potent membrane-disruptive antimicrobial activity in vitro

---

✅ Research-Only Classification

LL-37 is supplied strictly for controlled in-vitro laboratory research.
Not approved for human or animal administration, ingestion, injection, or therapeutic application.

---

If you’d like, I can also provide: