LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity

Fabisiak, Adam; Murawska, Natalia; Fichna, Jakub

doi:10.1016/j.pharep.2016.03.015

Cited by 114 publications

(75 citation statements)

References 88 publications

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“…LL-37 exhibits a broad spectrum of antimicrobial activity, several immunomodulatory effects, anticancer activities, and also chemotactic and pro-angiogenic properties (35, 40). It has been detected in several types of cells, tissues, and fluids, and along with other AMPs, such as β-defensins, plays a central role in mucosal defense (76).…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies

2017

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While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains.

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Section: Antimicrobial Peptidesmentioning

confidence: 99%

Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies

2017

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“…Initially discovered in human neutrophils, defensins are small cationic peptides that kill microbes in an oxygen-independent manner 189 . Defensins and cathelicidins function by inserting into the membranes of a broad range of prokaryotic cells, including gram-positive and gram-negative bacteria, fungi, protozoa, spirochetes, and enveloped viruses 187,190 . Once inside the microbial cell membrane, they form pores allowing the passage of anions through the membrane, thus depolarizing and killing the organism 191 .…”

Section: Physical Barriers Protecting the Gi Tractmentioning

confidence: 99%

Pathogenesis of NEC: Role of the innate and adaptive immune response

Denning

Bhatia

Kane

et al. 2017

Seminars in Perinatology

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Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC.

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“…This potential is, however, limited in some cases by the pleiotropic effects of the peptide [244]. For example, the peptide shows a variation in its sensitivity to cancer types, promoting proliferation, migration, and tumorigenesis in breast, lung, and prostate cancers through receptor signaling but suppresses proliferation and induces apoptotic and autophagic cell death in gastric cancer, colon cancer, and T-cell leukemia [107].…”

Section: Potential Applications Of Ph Dependent Antimicrobial Peptmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

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LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity

Cited by 114 publications

References 88 publications

Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies

Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies

Pathogenesis of NEC: Role of the innate and adaptive immune response

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

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