LL-37

Understanding LL-37: Your Body's Antimicrobial Peptide

What is LL-37?

LL-37 is a peptide (short chain of amino acids) that your body naturally produces as part of its infection-fighting system. Scientists have synthesized this peptide in the laboratory so they can study how it works and what effects it has on various biological systems. The name "LL-37" comes from the two leucine amino acids at the beginning and the total 37 amino acids in the chain.

LL-37 Peptide Structure

How Does LL-37 Relate to Your Immune System?

Your immune system has multiple layers of defense. The first line includes your skin, mucous membranes, and special immune molecules like LL-37. These work together to fight off bacteria, fungi, and viruses before they can cause infection. LL-37 is produced by epithelial cells (skin and tissue lining cells) and immune cells circulating in your blood.

What Makes LL-37 Special?

Unlike antibodies, which specifically target one pathogen, LL-37 works against a broad range of harmful microorganisms. It kills bacteria (both common types), fungi, and certain viruses. It also works alongside other immune molecules to enhance overall infection defense.

Beyond fighting infections, LL-37 does something even more interesting: it helps regulate your immune system's inflammatory response. Inflammation is necessary for fighting infection, but excessive inflammation causes tissue damage. LL-37 appears to help balance this response—turning up immune activity when needed, but toning it down when the threat is controlled.

Key Research Areas

Fighting Infections

LL-37 damages bacterial cell membranes, making it particularly effective against certain bacteria. It also boosts the activity of other immune enzymes. When skin becomes infected, LL-37 levels rapidly increase, helping control the infection.

Controlling Inflammation

Surprisingly, LL-37 plays a role in conditions like arthritis, psoriasis, and lupus. Rather than causing these conditions, elevated LL-37 appears to be the body's attempt to manage excessive inflammation. The evidence suggests LL-37 might actually help prevent these diseases from worsening.

Lung Health

When harmful substances like mold toxins enter the lungs, LL-37 production increases. This may be why some people with asthma or chronic lung disease have altered LL-37 levels. Researchers are exploring whether increasing LL-37 in the lungs could help manage these conditions.

Wound and Tissue Healing

LL-37 promotes epithelial cell growth and migration—essential processes for wound healing and tissue repair. It also helps form new blood vessels needed for tissue growth. This explains why chronic wounds sometimes lack adequate LL-37 levels.

Joint Protection

In arthritis, LL-37 levels increase in affected joints. Rather than causing damage, LL-37 appears to protect cartilage and reduce inflammatory markers, suggesting the body ramps up LL-37 as a protective response.

Intestinal Health

LL-37 helps maintain the intestinal barrier by promoting cell growth and reducing inflammation-induced cell death. It works with other immune peptides to enhance intestinal healing, potentially benefiting people with inflammatory bowel diseases.

Cancer Prevention

Early research suggests LL-37 may support immune cells in controlling certain cancers, possibly working through vitamin D-dependent mechanisms. This could explain the connection between vitamin D levels and cancer risk.

How Does LL-37 Work at the Molecular Level?

LL-37 works through several mechanisms. It directly damages bacterial membranes, binds to bacterial toxins that would otherwise trigger inflammation, and interacts with various cell surface receptors that activate immune responses. These multiple action pathways explain why LL-37 has such diverse biological effects.

Interestingly, Context Matters

LL-37's effects depend heavily on what's happening in the surrounding tissue. The same peptide can enhance immune activity in one situation and suppress it in another, depending on whether immune cells are already activated. This "smart" regulation may be why LL-37 appears protective in so many conditions.

Why Does LL-37 Vary Between Species?

Humans, mice, and other mammals all have cathelicidin peptides, but they differ in structure. These structural differences affect how the peptides bind to receptors and what effects they produce. Understanding these variations helps researchers understand how molecular structure determines biological function.

Current Research Directions

Scientists continue investigating how to best use LL-37 for therapeutic purposes. They're exploring optimal dosages, delivery methods (injection vs. inhaled), and which conditions might benefit most. They're also developing modified versions of LL-37 that might be even more effective than the natural peptide.

Key Points About LL-37

• LL-37 is your body's natural antimicrobial peptide
• It fights bacteria, fungi, and some viruses
• Beyond killing pathogens, it regulates inflammation
• It appears protective in inflammatory diseases rather than harmful
• It supports wound healing and tissue repair
• Its effects depend on the biological context
• Researchers are exploring therapeutic applications

References for Further Learning

Dürr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human cathelicidin: structure, function, and applications. Biochim Biophys Acta. 2006;1758(9):1408-1425. https://pubmed.ncbi.nlm.nih.gov/16716248/

Vandamme D, et al. A comprehensive summary of LL-37 and its derived peptides. Cell Mol Life Sci. 2012;69(20):3885-3908. https://pubmed.ncbi.nlm.nih.gov/22585085/

Nijnik A, Hancock RE. The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr Opin Hematol. 2009;16(1):41-47. https://pubmed.ncbi.nlm.nih.gov/19057201/

Overhage J, et al. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76(9):4176-4182. https://pubmed.ncbi.nlm.nih.gov/18591225/

Heilborn JD, et al. The cathelicidin peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcers. J Invest Dermatol. 2003;120(3):379-389. https://pubmed.ncbi.nlm.nih.gov/12603845/

Barlow PG, et al. Antiviral activity and increased host defense response of LL-37 in influenza virus infection. J Immunol. 2011;186(10):6166-6174. https://pubmed.ncbi.nlm.nih.gov/21460223/

Kahlenberg JM, Kaplan MJ. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol. 2013;191(10):4895-4901. https://pubmed.ncbi.nlm.nih.gov/24163488/

Mookherjee N, et al. Modulation of the TLR-mediated inflammatory response by LL-37. J Immunol. 2006;176(4):2455-2464. https://pubmed.ncbi.nlm.nih.gov/16456005/

Krasnodembskaya A, et al. Human cathelicidin peptide LL-37 promotes mesenchymal stem cell-mediated immunomodulation and tissue repair. Proc Natl Acad Sci USA. 2010;107(32):14292-14297. https://pubmed.ncbi.nlm.nih.gov/20660729/

Ramos R, et al. Wound healing activity of LL-37 peptide. Peptides. 2011;32(9):1849-1858. https://pubmed.ncbi.nlm.nih.gov/21763365/