LL-37 is an anti-microbial peptide. It has been shown to have antimicrobial activity against multiple Gram-positive and Gram-negative human pathogens. Antimicrobial peptides (AMPs) have the potential to serve as an alternative to antibiotics. It's simple, AMPs kill the microbial pathogens (the bugs). AMPs can possibly regulate bacteria/virus invasion and may control infection. It has been reported that AMPs could be used to activate the innate mucosal immune response in order to get rid of the infections. (Mucosal refers to the immune response at mucosal membranes of the intestines, the urogenital tract and the respiratory system, i.e., surfaces that are in contact with the external environment).
LL-37 belongs to the cathelicidin family of AMPs. It is released as a mature peptide when neutrophils (type of white blood cell) are stimulated. LL-37 is expressed in various cells and tissues such as circulating neutrophils, bone marrow cells, epithelial cells of the skin, cells in the gastrointestinal tract, as well as in the epididymis and lungs.
Production of LL-37 in macrophages is stimulated by vitamin D released by sunlight through the skin. LL-37 plays an important role in the first line of defense against infection and systemic invasion of pathogens at sites of inflammation and wounds. It is toxic to both bacterial and normal cells and is very resistant to proteolytic degradation.
Staphylococcus aureus, (staph for short), is one of the largest problems facing modern medicine, particularly since it has become resistant to a number of antibiotics. Research with LL-37 shows that it is effective against staph at nanomolar concentrations. It kills the bacteria both when it invades cells and when it is free, and is more effective than conventional antibiotics. These features make LL-37 of particular interest to the medical field and it is hoped that the peptide will be useful in treating chronic infections, such as those who have diabetes or immune system dysfunction. It has also been effective in treating Candida albicans and E. coli.
Several studies show that LL-37 is effective in treating certain cancer cell types. LL-37 inhibits gastric cancer cell proliferation by the activation of bone morphogenetic protein (BMP) signaling. However, overexpression of LL-37 was found to promote development and progression of ovarian, lung and breast cancers.
LL-37 and Tissue Healing
In addition to its ability to be anti-biofilm and antimicrobial, LL-37 plays an important role in regulating the balance of pro- and anti-inflammatory molecules. The balance between inflammation and tissue healing is a delicate one. Inflammatory responses are absolutely necessary if the body is to fight off invading pathogens. Unfortunately, these same inflammatory responses can prevent adequate healing, promote scar tissue formation, and even lead to autoimmune diseases if left unchecked. LL-37 appears to play a role in balancing inflammation with healing and at least part of that role is mediated through effects on macrophages.
Macrophages promote inflammation when foreign pathogens are detected. They do this by first detecting the pathogens and then sending signals to the rest of the body that a defense needs to be mounted. Once the tide shifts and the immune system begins to overtake that pathogens, macrophages begin producing a new set of signals that calm the inflammation so that the body can move to the next phase of healing. It turns out that peptides like LL-37 play an important role in reversing the activation of macrophages. The presence of LL-37 converts anti-inflammatory macrophages into pro-inflammatory macrophages.
The ability of LL-37 to inhibit biofilm formation is another promising feature with regards to the treatment of chronically infected wounds by S. aureus and P. aeruginosa. It’s anti-biofilm properties help to expose and clear the underlying bacteria. The peptide interaction with keratinocytes and fibroblasts also encourages wound closure.
Benefits of LL-37
- Broad spectrum antimicrobial activity against bacteria, enveloped viruses, and fungi
- Helps promote wound healing
- Can help control infection
- Can balance tissue inflammation
- Inhibits biofilm formation
LL37 is a multifunctional host defense peptide. Besides its antimicrobial and antibiofilm activity, it stimulates a complex group of responses in many cells, either directly or through modulation of cellular responses to microbial compounds and other immune mediators. Membrane-disrupting antimicrobial peptides provide broad-spectrum defense against localized bacterial invasion.
Serum LL-37 Levels Associated With Severity of Bronchiolitis and Viral Etiology.pdf
Dürr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 2006; 1758:1408–25
Currie SM, Findlay EG, McHugh BJ, et al. The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus. PLoS One 2013; 8:e73659
Schgler A, Muster RJ, Kieninger E, et al. Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37. Eur Respir J 2016; 47:520–30.
Mansbach JM, Piedra PA, Borregaard N, et al. Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis. J Allergy Clin Immunol 2012; 130:1007–8.e1.
Hsieh IN, Hartshorn KL. The role of antimicrobial peptides in influenza virus infection and their potential as antiviral and immunomodulatory therapy. Pharmaceuticals (Basel) 2016; 9:53.
Gwyer Findlay E1, Currie SM, Davidson DJ. Cationic host defence peptides: potential as antiviral therapeutics. BioDrugs. 2013 Oct;27(5):479-93. doi: 10.1007/s40259-013-0039-0.
Kościuczuk EM, Lisowski P, Jarczak J, et al. Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep. 2012;39(12):10957-10970. doi:10.1007/s11033-012-1997-x