**Background**
Periodontal diseases and deep tissue injuries, such as pressure ulcers, are characterized by persistent bacterial infections and impaired healing processes. These conditions often involve the infiltration of pathogens that disrupt tissue integrity and trigger excessive inflammatory responses. The formyl peptide receptor-like 1 (FPRL1) has emerged as a critical target in modulating the immune response and promoting the clearance of these pathogens. Activating FPRL1 can trigger immune cell chemotaxis and regulate the release of pro-inflammatory cytokines, which is essential for effective wound recovery and infection control. In this context, we will introduce a selective agonist of FPRL1 – LL-37 amide.
**Definition**
LL-37 amide is the carboxyl-terminal amidated form of the human antimicrobial peptide LL-37, which acts as a selective agonist of FPRL1 to exert bactericidal and immunomodulatory effects.
**In Vitro and In Vivo Studies**
According to the LL-37 amide description, the amidation modification of this peptide reduces its sensitivity to serum inhibition and significantly improves its stability and resistance to enzymatic degradation compared to natural LL-37. In terms of LL-37 amide in vitro activity, the peptide demonstrates potent antibacterial effects against both Gram-positive bacteria (e.g., Bacillus megaterium) and Gram-negative bacteria (e.g., Escherichia coli D21), with a minimum inhibitory concentration (MIC) against D21 of approximately 5 μM. Furthermore, it exhibits strong bactericidal activity against periodontal pathogens; specifically, it shows ED99 values of 8.7 μg/mL for Actinobacillus actinomycetemcomitans FDC-Y4 and 8.5 μg/mL for Porphyromonas gingivalis ATCC 33123 within 1 hour. Regarding cytotoxicity, the peptide is safe for eukaryotic cells within a concentration range of 0.1-10 μM, though toxicity increases above 10 μM.
Regarding LL-37 amide in vivo application, research has utilized the peptide in combination with chitosan hydrogels for topical administration. In a Staphylococcus aureus skin infection model using BALB/c mice, the application of 10 μg of LL-37 amide TFA significantly accelerated wound healing, enhanced bacterial clearance, and reduced inflammatory responses more effectively than free LL-37. Mechanistically, the peptide works by disrupting bacterial cell membrane integrity and inhibiting the release of inflammatory factors such as TNF-α, while simultaneously promoting angiogenesis. In conclusion, LL-37 amide is a stable, potent antimicrobial and immunomodulatory agent that holds promise for treating infection-related diseases and promoting tissue repair.
Keywords
LL-37 amide, Formyl Peptide Receptor (FPR), Bacterial, antimicrobial,cancer, Inhibitor, inhibitor, inhibit
References