Ll 37 Injection

LL-37 inserts into bacterial cell membranes through an amphiphilic alpha helix structure, forming pores or disrupting membrane integrity, leading to leakage of intracellular substances and cell death. For example, research on Staphylococcus aureus has shown that LL-37 can cause depolarization of cell membrane potential and ATP leakage, ultimately leading to bacterial death.LL-37 is the only Cathelicidin antimicrobial peptide present in the human body, synthesized and released by immune cells such as neutrophils and epithelial cells.

The amino acid sequence of LL-37 is:
LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES
Its molecular weight is 4.5 kDa, with an isoelectric point of 9.62, and it carries a positive charge at physiological pH. The secondary structure of LL-37 presents an amphiphilic alpha helix, with a hydrophobic region at the N-terminus and a hydrophilic region at the C-terminus. This structure allows it to simultaneously bind to the hydrophobic lipid layer and hydrophilic phospholipid head of bacterial cell membranes, forming transmembrane pores or disrupting membrane integrity, leading to leakage and death of cell contents. In addition, LL-37 can also inhibit bacterial growth by suppressing bacterial nucleic acid and protein synthesis, interfering with cell wall synthesis, and other mechanisms.

ll 37 Injection has inhibitory or bactericidal effects on Gram positive bacteria (such as Staphylococcus aureus and Streptococcus), Gram negative bacteria (such as Escherichia coli and Pseudomonas aeruginosa), fungi (such as Candida albicans), and viruses (such as HIV and influenza virus). Its antibacterial mechanism includes LL-37 binding to bacterial membrane anionic components (such as lipopolysaccharides, LPS) through positive charges, forming an alpha helical structure inserted into the lipid bilayer, leading to membrane disintegration or the formation of transmembrane pores (carpet model or circular pore mechanism). 

LL-37 is not only an antibacterial molecule, but also an important immune regulatory factor. Its functions include activating G protein coupled signals by binding to formyl peptide receptor like 1 (FPRL1), inducing neutrophil, monocyte, and T cell migration to the site of infection. In addition, LL-37 can promote the secretion of chemokines such as IL-8 and MCP-1, forming a positive feedback amplification immune response. During the acute infection phase, LL-37 activates TLR7/8/9 signaling in plasma cell like dendritic cells (pDCs), driving IFN - α secretion and Th17 differentiation, enhancing antibacterial immunity;

LL-37 plays a dual role in tumorigenesis and development, and its effect depends on tumor type and microenvironment: in ovarian cancer, lung cancer and breast cancer, LL-37 enhances tumor cell invasion and promotes epithelial mesenchymal transformation (EMT) by activating EGFR/ErbB-MAPK/ErbB2 pathway;

Meanwhile, LL-37 can recruit mesenchymal stem cells (MSCs) to secrete factors such as VEGF and IL-6, forming a pro angiogenic and immunosuppressive microenvironment that accelerates tumor progression. In melanoma, LL-37 inhibits tumor growth by enhancing antigen presentation and T cell infiltration.

Skin and soft tissue infection: The antibacterial and wound healing effects of LL-37 make it a candidate drug for treating burn wound infection and diabetes foot ulcer. In a clinical trial, LL-37 topical formulation significantly shortened wound healing time and reduced antibiotic use.
Respiratory tract infection: LL-37 inhalation formulation may be used to treat chronic infection of Pseudomonas aeruginosa in patients with cystic fibrosis. LL-37 can improve infection clearance by disrupting biofilms and enhancing antibiotic permeability.

Psoriasis: LL-37 is highly expressed in psoriatic lesions and activates TLR9 by forming complexes with its own DNA, driving pDCs to secrete IFN - α and Th17 differentiation. Antibodies targeting LL-37, such as neutralizing antibody IMS-1, have been shown in phase II trials to reduce PASI scores (with an average improvement of 40%).Atopic dermatitis (AD): Children with AD have reduced expression of TLR2 and LL-37, leading to impaired skin barrier function and increased risk of infection. Vitamin D can promote LL-37 expression through the TLR2 pathway, and in the future, LL-37 related drugs may be designed to assist vitamin D therapy for AD.

Ischemic heart disease: Shock wave treatment (SWT) can release LL-37 through mechanical pressure, activate TLR3 to induce vascular regeneration and ischemic myocardial regeneration, and inhibit myocardial scar formation. This discovery has opened up a new field for the application of antimicrobial peptides.
Alzheimer's disease (AD): LL-37 is an endogenous agonist of chloride channel protein 1 (CLIC1), which can activate CLIC1 channels, induce neurotoxic effects on glial cells, and induce AD like pathological phenotypes in mice. Intervention in CLIC1-LL-37 interaction may become a new target for AD treatment.