Cathelicidin – Its Structure, Function and the Role in Autoimmune Diseases

Abstract

Summary: 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.

Inflammatory mediators and lung abnormalities in HIV: A systematic review

“…An association between low cathelicidin levels and history of bacterial pneumonia has also been observed [36]. Cathelicidin, an innate response protein that acts as a cell signaling and chemotaxis molecule, serves as a natural antimicrobial against viruses, bacteria and fungi [61]. Although it can be expressed by numerous cell types (macrophage, mast cells, and airway epithelial cells), it is perpetually available within neutrophils [62–64].…”

“…Although it can be expressed by numerous cell types (macrophage, mast cells, and airway epithelial cells), it is perpetually available within neutrophils [62–64]. Upon stimulation of the exterior of the neutrophil, cathelicidin is released into the extracellular milieu triggering a cascade of events including induction of incoming neutrophils, recruitment of monocytes, eosinophils, mast cells and T lymphocytes and initiation of epithelial regeneration and remodeling [61,62,65]. High concentrations of cathelicidin can contribute to epithelial injury and destruction through overstimulation and overproduction of structural cells [62].…”

Quantitative Trait Locus Analysis of Protein and Oil Content in Response to Planting Density in Soybean (Glycine max [L.] Merri.) Seeds Based on SNP Linkage Mapping

“…Glyma.03G014600.1 encodes malate dehydrogenase (MDH), an important enzyme that catalyzes malic acid formation and is significantly affected by light stimulation, it is photo regulatory enzyme (Li et al, 1999). Malate is an important intermediate metabolite in plant cells, which are many biological functions in metabolic pathways (glyoxylate cycle, tricarboxylic acid cycle, glucose synthesis, amino acid synthesis, and redox stability), we know that these metabolic pathways are related to protein and oil synthesis (Minarik et al, 2002;Matsuda et al, 2010). Moreover, this enzyme is a key enzyme in the C4 pathway in Wheat (Hata and Matsuoka, 1987) and Soybean (Hao et al, 1991), which maintain a high photosynthetic carbon assimilation capacity when the light capacity and carbon dioxide content decrease.…”

Cyanobacteria and Eukaryotic Microalgae as Emerging Sources of Antibacterial Peptides

“…The success of AMPs is endorsed by their ubiquitous presence throughout evolution, crossing taxonomical kingdoms [ 25 ], even in those organism endowed with a robust and sophisticated antigen-specific immunity. In pluricellular organisms, AMPs may play additional roles out of their primeval function as deterrent for infection, such as messengers for communication among immune cells, angiogenesis, wound healing, autoimmunity [ 30 , 31 ], their dual role in inflammation [ 32 , 33 ], or even in sleep, among others [ 34 , 35 , 36 , 37 , 38 ].…”