What Is This LL-37 Stuff?
LL-37 is an antimicrobial peptide that kills invading microorganisms by disrupting their membranes. It is composed of 37 amino acids and is directly produced from the C-terminal of a bigger protein in your body known as a cathelicidin. The name “cathelicidin” refers to an antimicrobial peptide.
(The amino acid sequence begins with two leucines; this is the origin of the “double L” that appears at the beginning of the name.)
This cathelicidin, also known as hCAP18, is the ONLY naturally generated male cathelicidin that has ever been discovered, and it may be found in a variety of locations throughout your body, including the following:
Mucosal epithelial cells, neutrophils, monocytes, monocytes, granulocytes, natural killer (NK) cells, T and B lymphocytes, adipose fat, and nk cells are all responsible for the production of the peptide LL-37. Its expression is controlled by a number of endogenous variables, such as cytokines that promote inflammation and hormones that promote growth, in addition to a version of vitamin D that is active. (Source)
“LL-37 is expressed in many different types of tissue cells, such as melanocytes, specialized cells in the colon, airway, ocular surface, and genitals, in eccrine glands, Schwarz glands in the intestine, myelocytes, mesenchymal stromal cells (MSC), and cells of the testes.
The sole human cathelicidin is known as hCAP18, which stands for human 18 kDa cathelicidin antibacterial protein. Since its discovery in 1995, LL-37, the [host defence peptide] that it secretes, has been the subject of a great deal of research. It is considered to be a paradigm for the numerous functions that cathelicidin peptides play in host defence.
“In 1995, the human cathelicidin known as hCAP18 was separately reported by three distinct research groups. Using PCR probes that were based on porcine PR-39, one researcher was able to identify the pro-form of a peptide that they named FALL-39. The second group used oligonucleotide probes based on the rabbit sequence to search for the human equivalent of LPS-binding CAP18. Meanwhile, the third group directly isolated a 19 kDa protein from the specific granules of human neutrophils and then isolated its cDNA from a chronic myeloid leukaemia library.
“The human cathelicidin HDP, LL-37, an amphipathic -helical peptide, displayed a relatively medium-sensitive antibacterial activity and, surprisingly, the capacity to adopt this structure also in aqueous at physiological salt concentrations,” the researchers said.
AMPs have received a lot of attention and effort as potential new antimicrobials to treat microbial infections, particularly those caused by pathogens that are resistant to conventional antibiotics. This is due to the fact that these biomolecules provide several advantages over conventional antibiotics, such as the following:
(a) lower levels of resistance; (b) broad-spectrum activity with the least toxicity to the host; (c) synergistic effects on the antimicrobial activity of antibiotics; and (d) rapid killing. a) Lower levels of resistance; (b) Broad-spectrum activity with the least toxicity to the host; (c) Synergistic effects on the antimicrobial activity
As a result of these qualities, antimicrobial peptides (AMPs) are now being regarded the most promising choice to combat antibiotic resistance.
The workings of the LL-37 drug are as follows:
Antimicrobial peptides are able to interact with bacterial membranes in part due to the amphipathic structure that gives them this capacity. Cationic antimicrobial peptides are the most common kind because the vast majority of antimicrobial peptides contain a net positive charge.
The binding of these antimicrobial peptides to bacterial membranes is made more stable by the electrostatic interactions that take place between negative defensins and anionic bacterial membranes. After this, the membrane of the bacterium is broken, which results in the insertion of antimicrobial peptides into the membranes and, frequently, the creation of holes.
In conclusion, the binding of antimicrobial peptides results in the destruction of membrane potential, a modification in membrane permeability, and the leaking of metabolites, which eventually leads to the death of bacterial cells.
LL-37 has a chemotactic action, which means that it acts upon human peripheral blood monocytes, neutrophils, and T cells and induces movement in these cell types. It was demonstrated that it could modify the expression of hundreds of genes in monocytes and other cells, including the genes that code for chemokines and the receptors for those chemokines.
Human neutrophils that have been exposed to LL-37 display delayed apoptosis and an increase in the generation of reactive oxygen species.
Consequently, during an infection, it is reasonable to anticipate that LL-37, whether it is produced by the degranulation of neutrophils or secreted by other cells, will affect the innate immune response in a number of different ways.
When exposed to LL-37, cells that participate in inflammation are recruited, M1 macrophages are induced, and the stimulation of inflammatory responses, including activation of the inflammasome and generation of type I interferon, takes place. The production of type I IFN is increased when LL-37 is used to protect both RNA and DNA. This opens the door for the activation of endosomal TLR7 and TLR9, respectively. NETosis is promoted by anti-LL-37 autoantibodies, which in turn generates a source of more LL-37 DNA complexes. LL-37 is expressed on the surface of neutrophils, and it is identified by these autoantibodies.
Nevertheless, LL-37 possesses potent anti-inflammatory actions, such as inhibiting the activation of TLR4 receptors by lipopolysaccharide (LPS), lowering the levels of inflammatory cytokine responses, and blocking the invasion of and inflammatory responses to pathogenic microorganisms.
The Top 7 Positive Aspects of LL-37 for Your Health
If you do a fast search on PubMed, you will see that there have been around 1,776 research articles published on LL-37 between the years 1996 and the time that this article is being written.
Therefore, there must be a substantial quantity of data to back up the utilisation of this peptide in clinical settings such as hospitals and clinics.
The answer, in a word, is a resounding yes; this is true for virtually every single peptide that I discuss on this page.
The LL-37 Compound Is A Powerful Antibiotic
In spite of the fact that this is LL-37’s primary selling point, there has never been a research project conducted in people in which LL-37 was utilised as a direct antibacterial therapy.
However, it has been investigated both in living organisms and in test tubes using a wide variety of microorganisms, including:
When compared to medicines and silver nanoparticles, the LL-37 treatment for staphylococcus aureus demonstrated much faster bacterial clearance.
- LL-37 may be able to inhibit bacterial colonisation of Staphylococcus epidermidis, according to recent research.
- LL-37 was able to decrease the creation of biofilms by a multidrug-resistant strain of Escherichia coli, which is a necessary step for bacteria to take in order to acquire resistance to antibiotics.
- Pseudomonas aeruginosa: LL-37 was able to effectively prevent the production of biofilm against this organism
- Even with this small data set, it is clear that LL-37 has the potential to be an antibiotic effective against a wide variety of pathogens.
LL-37 Could Exert Antifungal Effects
To this far, LL-37 has mostly been evaluated for its effectiveness against two distinct kinds of fungal infections.
Aspergillus fumigatus is the first one, and LL-37 was effective to prevent infection in a rat trial with this fungus by numerous modes of action:
“Mice that were given LL37 treatment had decreased levels of fungus load, mild pathological damage, and lowered levels of proinflammatory cytokines,” the researchers said. In addition, LL37 transgenic mice (LL37+/+) were investigated to study the effects of endogenous LL37 in a model of A. fumigatus infection. These animals demonstrated a decreased susceptibility to A. fumigatus infection when compared with wild-type mice.
In addition, LL37 was found to have a protective effect in a mouse model of A. fumigatus infection that utilised mice with reduced immune systems. As a result, LL37 is able to prevent the spread of the A. fumigatus infection by directly attaching to mycelia and lowering the body’s inflammatory response.
After being treated with LL-37, changes in the integrity of the cell wall of C. albicans were seen using transmission electron microscopy, analysis of carbohydrates, and staining for beta-1,3-glucan. Additionally, the cell wall architecture of the pathogen was disrupted by LL-37’s presence.
Lastly, DNA microarray review and quantitative PCR revealed that sub-lethal densities of LL-37 thought to be mediated the expression of genes with a variety of functions, such as transporters, regulators for biological processes, responses to stress or synthetic impulse, and aetiology. These genes were found to be affected.