LL-37 (CAP-18) 10mg

The antimicrobial role of the sole human cathelicidin, LL-37, is invaluable. Aside from aiding in eradicating bacteria, LL-37 plays an important role in treating carcinoma, autoimmune disorders and wounds. Nevertheless, this article focuses on its antimicrobial properties. 

LL-37 peptides dwell in macrophages and polymorphonuclear leukocytes. Most recent studies discuss their effect on infected and inflamed lungs. This multifunctional cathelicidin is being developed for further therapeutic use.

Source: PubChem

• Sequence: -Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser
• Molecular Formula: C205H340N60O53
• vMolecular Weight: 4493.342 g/mol
• PubChem CID: 16198951
• vCAS Number: 154947-66-7
• Synonyms: CAP-18, Cathelicidin, antibacterial peptide LL-37

LL-37 and Inflammatory Diseases

LL-37 modulates the immune system, according to specific inflamed environment and cells that are involved. It plays an important role in autoimmune diseases that target joints, arteries, skin etc.

1. Reduces keratinocyte apoptosis
2. Diminishes levels of atherosclerotic plaques
3. Enhances IFN-alpha production
4. Down-regulates signaling through toll-like receptor 4 (TLR4)
5. Modifies the chemotaxis of neutrophils and eosinophils
6. Increases IL-18 production

How cells respond to LL-37 depends on conditions of the inflamed environment, thus it’s not consistent in its impact on the immune system. For instance, when unactivated lymphocytes are exposed to LL-37, they intensify their actions, whereas if they are already activated their response is reduced. 

Most recent evidence implies that LL-37 could prove to be an important regulator of unchecked inflammation in autoimmune disorders. Studies suggest that elevated levels of LL-37 correspond to lessening inflammation. 

Source: Karger

LL-37 Is a Potent Antimicrobial

Once infectious agents invade, a healthy immune system quickly responds. One of the first actions is rapidly increasing LL-37 levels to help subside the inflammation. Evidence suggests the importance of collaboration between LL-37 and other proteins, in regard to fighting pathogens. 

LL-37 binds to bacterial lipopolysaccharide (LPS), one of the most significant outer surface membrane parts most Gram-negative bacteria consist of. This trait proves fatal for many bacterial strains, which sparked interest in scientists who are exploring its usage regarding treating microbial infections exogenously. 

We stated that this cathelicidin focuses on targeting cell membrane constituents of gram-negative bacteria, but it is also capable of fighting against gram-positive bacteria. Being this versatile means we can potentially utilize LL-37 to treat staphylococcus bacteria induced infections, as well as other severe cases. This is because the peptide enhances lysozyme, a protein that plays a significant role in innate immunity.

LL-37 and Lung Disease

Almost all infections acquired by breathing in pathogens are severely contagious, hence why they require a certain approach when being treated. As well as other parts of our system, lung also responds to infectious agents with a defensive mechanism. While it can be enough to battle an infection, sometimes it proves powerless against toxic dust syndrome or the genesis of other respiratory diseases. 

On the other hand, it has been observed that LL-37 enhances the process of proliferating epithelial cells, facilitating wound closure. In the lungs specifically, the peptide serves a pivotal function in the way that it attracts airway epithelial cells to areas of injury, thus enhancing the healing process and development of vital blood vessels that supply nutrients to the tissue. LL-37 is not only a regulator of unchecked inflammation, but also crucial in regulating homeostasis within the airways.

Understanding LL-37 in Arthritis

Studies have been conducted in rats with rheumatoid arthritis, and the results suggest that joints affected by the disease have elevated levels of LL-37. The peptide seems to be associated with the pathological events of the arthritis, but it’s unclear whether it’s a causal factor or if the elevated number of the peptide is body’s attempt to regulate pathological processes. Important factors indicate that LL-37 might have a positive effect on inflammation, rather than being a causative agent. 

Currently, there is no evidence suggesting that LL-37, or any other cathelicidin for that matter, has a role in the development of inflammatory diseases. While this doesn’t completely rule out the possibility of the peptide being a causal factor, the overwhelming evidence suggests otherwise. For instance, the absence of LL-37 in animals with arthritis or lupus doesn’t impact the development of the disease. In other words, animals that lack the peptide exhibit a similar pathological progression – like those with LL-37, suggesting it being a coincidental occurrence. 

Research conducted in mouse models of arthritis indicates that peptides originating from LL-37 offer protective effects against collagen damage. When these peptides are directly administered to affected joints, two things can be noted. Firstly, there happens to be a reduction In disease severity and secondly, the levels of antibodies against type II collagens in the bloodstream also plummet. These findings imply that the sole human cathelicidin shows protective properties in arthritis, thereby explaining its elevated levels in inflamed tissue. 

Moreover, arthritis has been associated with the increased expression of toll-like receptor 3 in the fibroblasts present in synovial fluid. This factor is believed to contribute to the worsening of arthritis by elevating levels of inflammatory cytokines. The peptide has a property of binding to TLR4 and it can elicit either pro-inflammatory or anti-inflammatory effects. It is still unclear what exactly is its role in the context of TLR3 up-regulation, but research is ongoing. Idea that LL-37 could selectively diminish inflammation is entirely plausible, especially considering its observed capability to selectively reduce pro-inflammatory macrophage reactions.

LL-37 and the Intestine

The peptide exerts various effects within the intestine, as revealed by cell culture studies. For instance, LL-37 enhances the migration of cells crucial for maintaining the structure of the intestinal epithelial barrier. It reduces apoptosis, which slows down the progression of some inflammatory conditions. Conducted research indicates that LL-37 could serve as a beneficial supplementary treatment for inflammatory bowel conditions. Furthermore, the peptide has a potential to enhance the effects of antibiotics, mitigating the gastrointestinal side effects that often cause problems and stop us from using oral antibiotics. 

The peptide doesn’t act alone in the intestinal environment. LL-37 works together with human beta defensin 2 to enhance wound healing. The synergy of these peptides reduce TNF-related cell death and promote repairing and sustaining the intestinal epithelium. TNF-alpha inhibitors are very important in treating inflammatory bowel conditions, but they come with significant side effects, like increasing the risk of tuberculosis. This is why researching LL-37 and its potential in treating bowel inflammations is of the utmost importance, diminishing the dependence on TNF-alpha inhibitors.

LL-37 and Intestinal Cancer

Studies concerning the relationship between cancer and LL-37 have been conducted, yielding varied results. The peptide appears benefitial in fighting intestinal and gastric cancers, as well as oral squamous cell carcinoma. Since these effects are being mediated through a vitamin D-dependent pathway, it is evident that the previously noted correlation between vitamin D consumption and diminished risk of gastrointestinal cancer is further supported. 

LL-37 and Blood Vessel Growth

The initiation of prostaglandin E2 (PGE2) synthesis by LL-37 in endothelial cells is noteworthy. PGE2 is associated with inflammatory pain and blood vessel growth, and it exhibits varying effects. In endothelial cells, PGE2 induces angiogenesis, which is the process of blood vessel development. Given its implications in cancer progression, heart disease, stroke recovery, wound healing, and other critical processes, the intricate regulation of angiogenesis has been a focal point of extensive research. LL-37 offers tools that have a potential in bettering interventions regarding promoting blood vessel growth when needed, and reducing it in cases of cancer.

Fundamentally, LL-37 is the same peptide whether it’s in humans or in other mammals. However, the human version of the peptide has a different structural configuration, hence effecting receptor binding in a different way. Its obvious potential is not unnoticed by scientists, the peptide is continuously being exposed to various tests and studies in hope to better understand and finally utilize it for healing means. If we manage to manipulate protein production and use it for various useful functions, it would mean this branch of biochemistry would experience a revolution. 

In mice, LL-37 shows almost no side effects, displaying low oral bioavailability and yet excellent subcutaneous bioavailability. It’s imperative to recognize that dosages per kilogram in mice do not directly correlate to human equivalents. LL-37 purchased at Peptide Shop is strictly designated for educational and scientific research purposes, explicitly excluding human consumption. Acquisition of LL-37 should only be considered by individuals possessing valid research licenses.

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Daniela Xhindoli, PhD. operates from the University of Trieste, UNITS · Department of Life Sciences. Her focus surrounds gram-negative bacteria, the biological activities of LL-37 on simultaneously modulating pro-inflammatory and anti-inflationary pathways, and the antibacterial and antimicrobial effects of LL-37.

Daniela Xhindoli, PhD. is being referenced as one of the leading scientists involved in the research and development of LL-37. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Shop and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Daniela Xhindoli, PhD. is listed in  under the referenced citations.

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The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body.  These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease.  Bodily introduction of any kind into humans or animals is strictly forbidden by law.