LL-37 5mg

Introduction to LL-37

LL-37, also known as human cathelicidin antimicrobial peptide (CAMP), is a 37-amino-acid cationic peptide derived from the C-terminal region of the human cationic antimicrobial protein (hCAP18). It is the only member of the cathelicidin family in humans and plays a critical role in the innate immune system. LL-37 was first identified in neutrophils and is expressed in various tissues, including epithelial cells of the skin, gastrointestinal tract, respiratory tract, and leukocytes such as monocytes, T cells, and NK cells. Its primary function is to combat microbial infections, but it also exhibits immunomodulatory, anti-biofilm, and wound-healing properties, making it a promising candidate for therapeutic research.

Developed as a potential alternative to conventional antibiotics due to rising antimicrobial resistance, LL-37 has been studied for its broad-spectrum activity against bacteria, viruses, and fungi. Despite its potential, LL-37 has not yet received regulatory approval from agencies like the FDA for clinical use due to challenges such as high production costs, susceptibility to proteolytic degradation, and potential toxicity to human cells. Its applications are primarily in research settings, with ongoing investigations into its role in treating chronic infections, autoimmune diseases, and even certain cancers.

How LL-37 Works

LL-37 exerts its effects through multiple mechanisms, primarily targeting microbial pathogens and modulating immune responses. Its antimicrobial action involves disrupting bacterial cell membranes, particularly those of Gram-positive and Gram-negative bacteria. Unlike traditional antibiotics, LL-37 does not fit conventional membrane-disruption models (e.g., barrel-stave or toroidal pore formation). Instead, it remains parallel to the membrane surface, destabilizing it through a unique mechanism that leads to bacterial cell death. Additionally, LL-37 can penetrate bacterial cells to interact with intracellular targets, such as acyl carrier proteins, further enhancing its bactericidal effects.

Beyond direct antimicrobial activity, LL-37 modulates the immune system by influencing both pro-inflammatory and anti-inflammatory pathways. It interacts with receptors like formyl peptide receptor-like 1 (FPRL1) to chemoattract immune cells (neutrophils, monocytes, T cells) to infection sites. LL-37 also regulates toll-like receptor (TLR) signaling, suppressing pro-inflammatory cytokines (e.g., TNF-α, IL-4) while promoting anti-inflammatory cytokines (e.g., IL-10), which helps balance immune responses. Its ability to disrupt biofilms—complex microbial communities resistant to antibiotics—makes it particularly valuable for treating chronic infections, such as those in diabetic ulcers or cystic fibrosis.

LL-37 also shows antiviral and antifungal properties, inhibiting replication of viruses like herpes simplex virus (HSV) and fungi like Candida albicans by disrupting their membranes or interfering with intracellular processes. Additionally, it promotes wound healing by stimulating angiogenesis, epithelial cell proliferation, and collagen production, mediated through pathways like epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK/ERK).

Benefits of Using LL-37

LL-37 offers a range of potential therapeutic benefits, supported by preclinical studies and limited clinical data. Below are the key benefits:

• Broad-Spectrum Antimicrobial Activity: Effective against Gram-positive and Gram-negative bacteria (e.g., Staphylococcus aureus, Pseudomonas aeruginosa), drug-resistant strains, and fungi like Candida albicans. It also shows antiviral activity against viruses such as HSV and respiratory syncytial virus (RSV).

• Anti-Biofilm Properties: Disrupts biofilms in chronic wounds and infections, exposing underlying bacteria to immune responses and antibiotics, which is critical for conditions like diabetic ulcers and chronic sinusitis.

• Immune Modulation: Balances pro- and anti-inflammatory responses by suppressing excessive inflammation (e.g., downregulating TNF-α, IL-4) and promoting anti-inflammatory cytokines (e.g., IL-10), potentially aiding in autoimmune diseases like psoriasis and inflammatory bowel disease.

• Wound Healing and Tissue Repair: Promotes angiogenesis, epithelial cell proliferation, and collagen synthesis, accelerating wound closure in chronic wounds and supporting tissue regeneration.

• Potential Anticancer Effects: Inhibits proliferation of certain cancer cells (e.g., colon and gastric cancer) by inducing apoptosis via caspase-independent mechanisms and activating bone morphogenetic protein (BMP) signaling, though it may promote progression in cancers like ovarian and lung cancer.

• Support for Chronic Conditions: Shows promise in managing infections in conditions like cystic fibrosis and tuberculosis when combined with agents like vitamin D, and may improve lung function in inflammatory lung diseases.

Despite these benefits, LL-37’s clinical use is limited by challenges like high cost, reduced activity in physiological environments, and potential toxicity, necessitating further research and optimization.

Certificate of Analysis

LL-37 5mg- COA – FYP

The following technical details outline the properties of LL-37 5mg, providing a scientific snapshot of the peptide.