LL37 antimicrobial peptide: Structure and function

ABSTRACT

The human cathelicidin LL-37 plays a major role in the innate immune system for protection against bacterial infections. LL-37 can interact with molecules of the cell wall, perforate cell membranes, and finally lead to bacterial cell death. Moreover, LL-37 participates in immune regulation, chemotaxis of immune cells, and tissue repair. This peptide is produced by white blood cells (mainly neutrophils) and different epithelial cells (in the testicles, epidermis, intestinal system, respiratory system), and may be detected all over the body. LL-37 peptide has dual effects a) it can increase inflammation and immunological responses and possess anti-infective and anti-cancer properties;b) it can suppress inflammation and enhance carcinogenesis. LL-37 is related to the risk of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis atherosclerosis, and psoriasis. This peptide binds to self-DNA, and acts as an autoantigen. On the other hand, targeting the antiviral and immunomodulatory activities of LL37 peptide can reduce virus transmission and pathogenicity such as human immunodeficiency virus (HIV-1) and the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This peptide and its variants can directly attach to HIV-1 reverse transcriptase and inhibit its function in a dose-dependent approach. Moreover, in silico studies showed the potency of LL-37 as a therapeutic agent against SARS-CoV-2 infection. It is interesting that vitamin D, a candidate preventive molecule against coronavirus disease 2019 (COVID-19), can upregulate the expression of LL-37. The LL-37 cationic peptide can also penetrate the membrane of eukaryotic cells likely through lipid rafts. Indeed, it can transport the nucleic acid to endosomes, and facilitate oligonucleotide delivery to the cells. Regarding major functions of LL-37 peptide in body, this review will concentrate on its structure and functions as the only cathelicidin-derived defensive peptide identified in human.