What is LL-37?
LL-37, also known as CAP-18 (tensin-activated antimicrobial protein 18), is an antimicrobial peptide expressed in nearly all tissues and organs. It is produced by many cell types, including macrophages, airway epithelial cells, skin and ocular epithelial cells, and natural killer (NK) cells. 

Since its discovery in 1995, LL-37 has been studied in a number of ways. These studies have shown that LL-37 has anticancer effects in colon and gastric cancer. This natural peptide may also modulate the development of inflammatory and autoimmune diseases. 

LL-47 has been reported to exert a protective effect in a mouse model of collagen-induced arthritis. It has also been found to kill gram-negative bacteria through direct antimicrobial activity as well as regulation. In addition, it has been shown to promote wound closure in lung disease. 

LL-37 has also been shown to downregulate signaling of specific Toll-like receptors (TLRs), thereby reducing the production of pro-inflammatory cytokines. It also exhibits anti-inflammatory effects, primarily by blocking signaling in Gram-negative bacteria. 

The following are the functions that LL-37 has been shown to have:

Regulates the Type 1 Interferon Response
Type 1 interferons (INFs) are polypeptides secreted by infected cells. Research has shown that they can program and influence the development of both innate and adaptive immunity. Type 1 interferons can also modulate antigen presentation, regulate the function of natural killer (NK) cells, and inhibit viral pathogens. 

Regulates TLR Function

Toll-like receptors (TLRs) are important mediators of intestinal inflammatory pathways. LL-37 has been shown to downregulate signaling through TLR4 by binding to its ligand LPS. This results in reduced levels of pro-inflammatory cytokines when LL-37 and LPTS are present simultaneously.

Regulates inflammation

LL-37 has both pro-inflammatory and anti-inflammatory functions. This difference may be explained by the disease context and the microenvironment in which it is present.

Regulates cell death

LL-37 may promote or inhibit cell death, depending on the cell type involved and the environment in which it is mimicked. For example, higher doses of this peptide induce necrotic cell death in neutrophils. However, in other cells, it exhibits anti-apoptotic effects.

Exerts antimicrobial activity

LL-37 has been shown to have antimicrobial activity against bacteria, viruses, fungi, and parasites. Low concentrations of this peptide can prevent the formation of biofilms, while high concentrations can disrupt existing biofilms. Infections associated with biofilms may result in death. 

Induces angiogenesis

Angiogenesis, the formation of new blood vessels, is necessary for normal growth and development. It is also essential for wound healing. 

LL-37 research

The following is a summary of the current research on LL-37. The information provided in this section is for educational purposes only. It does not constitute medical advice. LL-37 peptides sold by PureRawz are for laboratory, educational, and scientific research purposes only.

LL-37 and Cancer

Several studies have shown that LL-37 plays an important role in human cancer.

This peptide has been found to play an anti-cancer role in colon cancer, gastric cancer, hematological malignancies (cancers that begin in blood-forming tissues such as the bone marrow), and oral squamous cell carcinoma (cancers that occur in the mouth). 

However, its anti-cancer effects are not all tumor-killing. LL-37 has also been found to induce the development of cancers such as ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, and lung cancer. More research is needed to further explore the specific effects of this peptide on cancer. 

LL-37 and Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that affects the joints of the hands, wrists, and knees.

According to studies, LL-37 inhibits the development of this disease by downregulating pro-inflammatory cytokines. Additionally, low doses of this peptide have been shown to reduce joint inflammation in mice with arthritis.

Another preclinical study reported that an LL-37-derived peptide provided protection in a mouse model of collagen-induced arthritis. The peptide, an internal fragment of LL-37, reduced disease severity and significantly lowered serum antibody levels against type II collagen.

LL-37 and Psoriasis
Psoriasis is a disease that causes thick, red plaques and silvery scales to appear on the skin.

Preclinical studies have shown that LL-37 induces apoptosis of keratinocytes in a psoriasis model. Keratinocytes are the main cell type in the outermost layer of the skin, accounting for approximately 90% of the cells in the skin's outermost layer. Psoriasis is characterized by keratinocyte hyperplasia, which LL-37 prevents. 

However, while the above studies demonstrated the anti-inflammatory activity of LL-37 in psoriatic skin, other studies have highlighted its pro-inflammatory effects. Therefore, studies in treated patients may provide a better understanding of the role of LL-37 in psoriasis. 

LL-37 and Bacteria

In preclinical studies, LL-37 has demonstrated moderate antibacterial activity against a variety of gram-negative and gram-positive bacteria that cause skin infections. 

LL-37 has been reported to kill bacteria through direct antibacterial activity as well as modulation of the immune system (immunomodulation). Direct effects include disruption of the bacterial membrane, which compromises cell integrity and ultimately leads to cell death.

Immunomodulatory activity includes induction of cell migration, proliferation, and differentiation. However, challenges remain before LL-37 can gain regulatory approval as an antibacterial agent. These challenges include high cost and low activity in physiological environments.

LL-37 and the Intestine

Cell culture studies have shown that LL-37 has multiple effects, including increasing migration of cells required for maintenance of the intestinal epithelial barrier and reducing cell death in intestinal inflammation. 

LL-37's role in the intestine makes it a potential candidate for the treatment of acute intestinal infections such as inflammatory bowel disease.

LL-37 and COPD

Chronic obstructive pulmonary disease (COPD) refers to a group of diseases that cause airflow obstruction and breathing-related problems. Approximately 16 million Americans suffer from this lung disease.

According to a clinical study of COPD patients, COPD patients who were at higher risk of frequent exacerbations had lower plasma LL-37 levels than healthy controls. Therefore, low levels of this peptide may be a predictor of exacerbation risk in COPD patients.

LL-37 and toxic dust syndrome

Organic dust syndrome is common among agricultural workers. It is characterized by fever and flu-like symptoms that develop 4 to 12 hours after exposure.

In vitro studies have shown that bacterial lipopolysaccharide (LPS) plays an important role in the pathogenesis of ODTS. This is important because LL-37 has been shown to neutralize this LPS and therefore has the potential to be used as a therapeutic agent for serious bacterial infections.

FAQ

Is LL-37 an antimicrobial peptide?

LL-37 is the only human member of the antimicrobial peptide family. Antimicrobial peptides are antimicrobial peptides (AMPs) found in humans and other species, such as farm animals. They are part of the immune system and protect the body from microbial attacks by viruses, bacteria, and fungi.

What does LL-37 do in the lungs?

Natural LL-37 has been shown to have multiple cellular activities in the lungs, such as killing of a wide range of microorganisms, cytotoxicity to epithelial cell proliferation, and angiogenesis. More research is needed to understand how normal lung tissue responds to LL-37.