Molecular Formula: C205H340N60O53
Molecular Weight: 4493.33 g/mol
PubChem: CID 16132341
CAS Number: 154947-66-7
What is LL-37 Peptide?
LL-37 is the only known human Cathelicidin is a big protein family where the members exhibit diverse functions. These peptides, essentially produced by macrophages and polymorphonuclear leukocytes (both types of white blood cells), have bactericidal action. They have been found to have shown other substantial effects as well. The entire group is often referred to as antimicrobial peptides (AMPs). LL-37 in particular has been found to play significant roles in autoimmune disease, cancer, and wound healing.
LL-37 Peptide Research
LL-37 and Inflammatory Diseases
LL-37, although essentially known to be an antimicrobial peptide, is also involved in different inflammatory diseases such as lupus, rheumatoid arthritis, psoriasis and atherosclerosis. LL-37 plays diverse immune system modulating behaviors based on the type of cells involved and the local inflammatory environment. It has been observed to:
– reduce apoptotic death of keratinocytes,
– improve IFN-alpha synthesis,
– suppress signaling through toll-like receptor 4 (TLR4),
– modify chemotaxis of neutrophils and eosinophils,
– trigger IL-18 production, and
– reduce levels of atherosclerotic plaques.
Interestingly, CAP-18 stimulates the immune system in a different manner depending on the trigger. Cell culture studies have highlighted the importance of inflammatory environment in determining the immune response to LL-37. T-cells, improve their inflammatory actions because of LL-37 when they are not activated but minimize the inflammatory action when already activated. The peptide appears to mediate homeostasis of immunological response thus controlling it from being hyperactive when the body is suffering from infection. It helps to control levels of inflammation in autoimmune diseases. There is a strong correlation between the levels of the peptide and the extent of the disease. Initially, CAP-18 was thought to promote autoimmune disorder but recent results have shown it helps to abate the damage. High levels of the peptide thus help to check further increase inflammation.
LL-37 Is a Potent Antimicrobial
It is an important biomolecule of the innate immunity and is one of the initial proteins to get activated when faced with an infection. Research in skin infections shows that the peptide, though present in very less amounts in the skin, accumulates very fast when invading pathogens are present. It works in conjunction with other proteins, like human beta-defensin 2 to fight infection.
LL-37 binds to bacterial lipopolysaccharide (LPS) of the outer membrane of gram-negative bacteria. LPS is critical for the membrane integrity of these bacteria. The ability of LL-37 to bind to and interfere with LPS makes it toxic for certain bacteria. Thus it has potential to be used exogenously to treat serious bacterial infections in people.
LL-37 is powerful against gram-positive pathogens as well thereby treating staph infections and other serious bacteria. In vitro research indicates that CAP-18 improves the effects of lysozyme which destroys gram-positive bacteria like Staph aureus.
LPS, is found in a number of different organisms and, in certain cases, becomes airborne when an environment is contaminated by mold or other fungi. Normal lung tissue responds by producing mucus upon LPS inhalation. Unfortunately, the response is often insufficient to intercept toxic dust syndrome and respiratory diseases like asthma and COPD to name a few. LL-37 is being considered as an inhaled treatment for toxic dust syndrome.
LL-37 promotes proliferation of epithelial cells and closure of wounds in lung diseases. The peptide attracts airway epithelial cells to sites of injury and helps vascularization, wound healing and supply of nutrition to the newly formed tissue. Thus the peptide mediates homeostasis in airways like in immune function.
Understanding LL-37 Peptide in Arthritis
Research in rats shows high LL-37 level in joints of rats suffering from rheumatoid arthritis. Interestingly, it is yet unknown if is the cause or cure for the condition. However, several findings indicate the therapeutic ability of the peptide in inflammation.
LL-37 deficiency does not change the outcomes in animal models of arthritis or lupus. Animals expressing the peptide thus show the same disease outcome as those which are lacking in the peptide. These results prove that the physiological reactions in presence of enhanced levels of cathelicidins in arthritis are incidental.
Peptides derived from LL-37 reduce collagen damage which occurs in inflammatory arthritis. Direct introduction of these peptides to arthritic joints in rats reduces both the severity of the disease as well as serum levels of antibody against type II collagen. Direct involvement of interleukin-32 (IL-32) in the severity of inflammatory arthritis has been reported. LL-37 and its derivatives regulate the level of IL-32 response. Hence, it would be reasonable speculation that the peptide is actually protective in this disease scenario.
Synovial fluid fibroblasts increase toll-like receptor 3 levels which in turn worsens the arthritic condition by increase of inflammatory cytokine expression. LL-37 interacts with TLR4 and either promotes pro-inflammatory or anti-inflammatory outcomes. It is yet to be confirmed if CAP-18 mediates the same effect in backdrop of increased TLR3. The peptide has selectively decreased pro-inflammatory macrophage responses in earlier studies, thus proving its regulation of inflammation to be selective.
Intestine and Intestinal Cancer
Cell culture-based findings have revealed multiple functions of LL-37 in the intestine. The peptide improves migration of cells necessary for epithelial barrier maintenance of the intestine. LL-37 also reduces apoptosis when there is an intestinal inflammation, helping to decline the causes of inflammation and the associated pathogenesis. The peptide can behave as a useful adjuvant for treatment of inflammatory bowel conditions post intestinal surgery, during acute intestinal infections a well as for oral antibiotic therapy thus preventing GI side effects.
LL-37 pairs with human beta-defensin 2 to help in wound healing. In vitro work indicates that the peptides work simultaneously for repair and maintenance of the intestinal epithelium while decreasing TNF-related cell death. TNF-alpha inhibitors, in spite of being the principal drugs for treatment of inflammatory bowel conditions, have various adverse side effects. They increase the chances of tuberculosis infection to a great extent. LL-37 based treatment will thus reduce the dependence on TNF-alpha inhibitors and thereby mortality rate.
The use of the peptide in cancer treatment has generated mixed reviews. However, it was found to be effective in intestinal, gastric, and oral carcinomas associated with smoking and tobacco use. The treatment is vitamin D dependent as vitamin D promotes anti-cancer function of tumor-associated macrophages through CAP-18.
Blood Vessel Growth
The peptide helps to produce prostaglandin E2 (PGE2) in endothelial cells. In endothelial cells, PGE2 promotes the development of blood vessels via a process called angiogenesis. It is crucial to regulate angiogenesis as it impacts cancer development, stroke outcomes, heart disease, wound healing, and more. LL-37 helps to study angiogenesis in-depth to promote it in cardiac disease and discourage cancer milieu.
Ongoing CAP-18 Peptide Research
The peptide varies in the structure of its human isoform compared to other animals. This increases its functional versatility by allowing interaction with different receptors. This feature helps scientists to study the impact of amino acid modulation to achieve specific functional outcomes.
LL-37 shows minimal to moderate side effects, low oral bioavailability and excellent subcutaneous bioavailability in murine models. The dosage (per kg) in mice does not match up to humans. LL-37 is sold at Biotech Peptides only for educational and scientific research and not for human consumption.
Only licensed researchers can buy LL-37 peptide.