Immunology researchers may be interested in learning how relevant the LL-37 peptide might impact their studies. The immune response relies on the endogenous peptide LL-37. Injuries and infections appear to trigger the synthesis of this peptide, which is believed to be essential for regulating immunological activities and accelerating wound healing. So far, research has suggested that LL-37 may have many characteristics, such as:
- Potential immune function regulation
- Potential faster recovery from injuries
- Potential combative action against microbes
This professional guide will help you discover the details of LL-37’s biological activities, research findings, and usage optimization.
LL-37 Peptide: What is it?
LL-37 (CAP-18) is a naturally occurring peptide in the class of antimicrobial peptides (AMPs). Of all the amphibians, defensins and cathelicidins are the most common. The cathelicidin family of antimicrobial peptides has only one member—LL-37—in the organism. It is derived from a bigger protein called the cathelicidin antimicrobial protein and has 37 amino acids.
Most immune cells, skin, gastrointestinal tract, respiratory tract, and testis epithelial cells all appear to express LL-37 because of their significance for immune defense. Monocytes, neutrophils, T-lymphocytes, NK cells, and B-lymphocytes are the particular cell types that express the peptide. According to research, LL-37 seems to have other potentially protective functions, such as:
- Controlling the organismțs inflammatory reaction
- Calling upon adaptive immune system cells (such as CD4 T lymphocytes) to infected or injured areas
- Interacting with and removing from the organism foreign substances like bacterial toxins
- Helping wounds heal by encouraging re-epithelialization
Research into these hypothetical impacts is still ongoing. Studies suggest that LL-37 may be activated in response to various pathogens, trauma, exposure to ultraviolet light, and the breakdown of various biological barriers. Studies have indicated that Vitamin D-dependent processes may be one of the primary ways the organism may control LL-37 expression in various cell types. Therefore, vitamin D deficiency could affect the LL-37 response.
You may use LL-37 as reference material for your lab work, and researchers are now investigating its potential in other cell lines and in vitro models. However, the vast lack of preclinical and clinical assessment means it is not yet authorized for use in humans.
LL-37 Peptide and Wounds
Experimental studies have suggested potential following the exposure of LL-37 on injured tissues, and the compound is now being studied for its potential in wound healing.
A study evaluated the potential of LL-37 in the context of chronic venous ulcers. Various concentrations of the peptide, as well as a control group, were evaluated for impact. The lowest concentration group suggested a significant increase in cell regrowth and healing compared to the control, whereas the highest and second highest concentration groups appeared to have a decrease in ulcer size of 68% and 50%, respectively.
In a separate experiment, researchers observed that LL-37 exposure may have suggested a trend toward less bacterial colonization and a consistently higher rate of developing new blood vessels and tissue.
An experiment known as HEAL assessed the effectiveness of LL-37 in combination with compression in venous ulcer tissue. Researchers hypothesized that the more large and proliferated ulcer cultures appeared to have benefited significantly after four weeks of exposure to the peptide at a consistent concentration.
LL-37 Peptide and the Immune System
According to researchers, LL-37 may affect the immune system’s ability to fight infections caused by viruses and bacteria. Below are a few of the most high-profile studies involving this concenr.
According to one study, LL-37 appears to help the immune system deal with rotaviruses and other viruses that primarily employ double-stranded RNA molecules (dsRNA) for their genetic material. This heightened immune response mechanism may result in better protection against viral infections.
Another investigation evaluated how LL-37 may affect the activation of mast cells, an important part of the immune system’s response to pathogens. By directly stimulating mast cells, LL-37 has been hypothesized to cause degranulation and the release of pro-inflammatory cytokines. It has also been theorized to function as a strong chemoattractant for mast cells.
LL-37 Peptide and Bacteria
Initial testing has suggested that LL-37 may exert action against various bacteria. Although there have not been many studies evaluated LL-37’s bactericidal properties, preclinical research has suggested that the peptide may protect several infection models:
One study examined rats given isotonic sodium chloride, LL-37, or three different antibiotics to see how well they worked against sepsis, a widespread illness. Although all the approaches appeared to have decreased mortality, LL-37 seemed equally effective as the antibiotics while producing far lower amounts of endotoxin and inflammation.
Another research on murine sepsis reported that LL-37 may have increased the survival rate of sick mice by lowering inflammation and suppressing macrophage pyroptosis, a cell death process linked to inflammation and activated by pro-inflammatory signals. In addition to preventing sepsis, LL-37 was hypothesized to increase the production of antimicrobial microvesicles (ectosomes) by neutrophils.
The protective characteristics of the peptide were speculated in a research that examined the impact of LL-37 on mice with gastrointestinal Escherichia coli infection. Loss of weight, intestinal injury, and epithelium apoptosis were all hypothesized to be mitigated by LL-37. Additionally, it appeared to have reduced inflammatory infiltration in the colon and jejunum and reduced levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) while increasing levels of the anti-inflammatory cytokine IL-10.
References
[i] Ridyard, K. E., & Overhage, J. (2021). The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent. Antibiotics (Basel, Switzerland), 10(6), 650. https://doi.org/10.3390/antibiotics10060650
[ii] Mahlapuu, M., Sidorowicz, A., Mikosinski, J., Krzyżanowski, M., Orleanski, J., Twardowska-Saucha, K., Nykaza, A., Dyaczynski, M., Belz-Lagoda, B., Dziwiszek, G., Kujawiak, M., Karczewski, M., Sjöberg, F., Grzela, T., Wegrzynowski, A., Thunarf, F., Björk, J., Ekblom, J., Jawien, A., & Apelqvist, J. (2021). Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 29(6), 938–950. https://doi.org/10.1111/wrr.12977
[iii] Johansson, J., Gudmundsson, G. H., Rottenberg, M. E., Berndt, K. D., & Agerberth, B. (1998). Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. The Journal of biological chemistry, 273(6), 3718–3724. https://doi.org/10.1074/jbc.273.6.3718
[iv] Miranda, E., Bramono, K., Yunir, E., Reksodiputro, M. H., Suwarsa, O., Rengganis, I., Harahap, A. R., Subekti, D., Suwarto, S., Hayun, H., Bardosono, S., & Baskoro, J. C. (2023). Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Archives of dermatological research, 315(9), 2623–2633. https://doi.org/10.1007/s00403-023-02657-8
[v] Nagaoka, I., Tamura, H., & Reich, J. (2020). Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model. International journal of molecular sciences, 21(17), 5973. https://doi.org/10.3390/ijms21175973
[vi] Grönberg, A., Mahlapuu, M., Ståhle, M., WhatelySmith, C., & Rollman, O. (2014). Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 22(5), 613–621. https://doi.org/10.1111/wrr.12211
[vii] Fang, X., Nong, K., Wang, Z., Jin, Y., Gao, F., Zeng, Q., Wang, X., & Zhang, H. (2023). Human cathelicidin LL-37 exerts amelioration effects against EHEC O157:H7 infection regarding inflammation, enteric dysbacteriosis, and impairment of gut barrier function. Peptides, 159, 170903. https://doi.org/10.1016/j.peptides.2022.170903
[viii] Bąbolewska, E., & Brzezińska-Błaszczyk, E. (2015). Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response. Cellular immunology, 293(2), 67–73. https://doi.org/10.1016/j.cellimm.2014.12.006
