Cathelicidin-its structure, function and the role in autoimmune diseases

Abstract

Antimicrobial peptides are widely distributed in nature, and they are found in both Prokaryotes and Eukaryotes. Due to their characteristics, structure, functions and mode of action, they are divided into several groups. The only member of this family occurring in humans is cathelicidin-LL-37. It is produced as an inactive hCAP18 propeptide. The propeptide's C-terminal fragment becomes a mature peptide subsequently to its enzymatic cleavage. LL-37 contains 37-amino acid residues, folds into α-helical structure and has amphipathic properties. Cathelicidin mechanism of action consists in the binding of LL-37 to the bacterial phospholipid membrane until a threshold concentration is reached, followed by the cytoplasm disintegration and leakage, and, finally, cell death. The peptide is expressed in several cells, for instance in the epithelial cells of testis, keratinocytes in the skin, leukocytes, monocytes, neutrophils, as well as T, B, and NK cells. Cathelicidin is a multifunctional molecule. It can serve as a mediator in inflammatory processes and/or as a natural antibiotic against Gram-negative and Gram-positive bacteria, viruses, and fungi. It is chemotactic for mononuclear cells, neutrophils, eosinophils, mast cells and T lymphocytes. LL-37 induces expression of chemokines, neutralises endotoxins, stimulates angiogenesis and apoptosis, as well as it boosts wound healing. Recent data have revealed an important role of LL-37 in the pathogenesis of systemic lupus erythematosus due to an impaired degradation of components in the neutrophil extracellular traps.