LL-37 is the only member of the cathelicidin family of antimicrobial peptides (AMPs) found in humans. It is a 37-amino acid, amphipathic α-helical peptide that serves as a critical component of the innate immune system.
Key Functions and Characteristics
- Antimicrobial Activity: LL-37 exhibits broad-spectrum activity against bacteria (Gram-positive and Gram-negative), fungi, viruses, and parasites. It works by disrupting negatively charged microbial membranes, leading to cell death.
- Immunomodulation: Beyond direct killing, it regulates leukocyte chemotaxis (attracting immune cells to infection sites), modulates cytokine production, and influences inflammatory responses.
- Wound Healing: It promotes re-epithelialization and wound healing by stimulating the migration of keratinocytes and inducing angiogenesis (the formation of new blood vessels).
- Antiviral Properties: Recent studies have highlighted its potential against viruses, including inhibiting SARS-CoV-2 infection by blocking the receptor-binding domain of the S1 spike protein.
- Role in Cancer: LL-37 plays a complex, dual role in cancer. It can exhibit anticancer effects by inducing apoptosis in certain cells (e.g., colon cancer) but has also been implicated in promoting carcinogenesis in other tissues like the breast and lungs.
Technical Specifications
- Amino Acid Sequence:
LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES. - Molecular Weight: Approximately 4493.37 Da.
- Source: It is generated through the extracellular cleavage of the C-terminal end of the hCAP18 proprotein, primarily by serine proteases.
- Production Sites: Expressed in epithelial cells (skin, respiratory, gastrointestinal tracts) and various immune cells like neutrophils, monocytes, and T cells.
Clinical Implications
While LL-37 is a potent host defense molecule, its dysregulation is linked to various conditions. For instance, overabundance is associated with inflammatory skin diseases like rosacea and psoriasis, while a lack of LL-37 can contribute to chronic non-healing ulcers. Research is ongoing to develop LL-37-based therapies, though challenges like high production costs and susceptibility to proteolytic degradation remain.
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