LL-37, the only human member of the cathelicidin family of antimicrobial peptides.

https://www.mastocytosis.com.au/downloads/Mast-cells-inflammation-BBA-2010.pdf

Mast cells and inflammation

Cationic host defence peptides (CHDP), also known as antimicrobial peptides, are naturally occurring peptides that can combat infections through their direct microbicidal properties and/or by influencing the host's immune responses. The unique ability of CHDP to control infections as well as resolve harmful inflammation has generated interest in harnessing the properties of these peptides to develop new therapies for infectious diseases, chronic inflammatory disorders and wound healing. Various strategies have been used to design synthetic optimized peptides, with negligible toxicity. Here, we focus on the progress made in understanding the scope of functions of CHDP and the emerging potential clinical applications of CHDP-based therapies.

/pdf/antimicrobial-host-defence-peptides-functions-and-clinical-48oa63nlrk.pdf

Antimicrobial host defence peptides: functions and clinical potential

Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.

/pdf/antimicrobial-peptides-key-components-of-the-innate-immune-1yqple1gft.pdf

Antimicrobial peptides: key components of the innate immune system

The last decade led to the discovery and characterization of several human β-defensins. Analysis of genomic information indicates that the number of β-defensin-like molecules encoded by the human genome may number in the tens. Growing interest in β-defensins steadily enhances our knowledge about various aspects of their gene location, expression patterns and the transcription factors involved in their regulation in vivo. The hallmark property of β-defensins, their antimicrobial activity, is clearly only the tip of the iceberg in the extensive network of inter-relations within the immune system in which these peptides function. Structural studies of β-defensins provide the molecular basis for a better understanding of their properties, functions and their potential for practical applications. In this review, we present some recent advances in the studies of human β-defensins, with an emphasis on possible correlations between their structural and functional properties.

Human β-defensins

Synergistic effect of antibacterial agents human β-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

Antimicrobial peptides human b-defensins (hBD) are mainly produced by epithelia of several organs including skin, and participate in innate immunity by killing invading pathogens Besides their microbicidal activities, hBD activate several inflammatory and immune cells Since hBD are generated by tissues where mast cells are present, we hypothesized that these peptides could activate mast cells In this study, we demonstrated that both hBD-3 and hBD-4 induced mast cell degranulation, prostaglandin D2 production, intracellular Ca 2+ mobilization and chemotaxis Furthermore, hBD-3- and hBD-4-induced activation of mast cells was suppressed by pertussis toxin and U-73122, inhibitors for G protein and phospholipase C, respectively We further revealed that hBD-3 and hBD-4 increased vascular permeability in the skin, which was dependent on the presence of mast cells, because hBD-3 and hBD-4 failed to enhance vascular permeability in mast cell-deficient Ws/Ws rats We also demonstrated that hBD-3 and hBD-4 induced phosphorylation of MAPK p38 and ERK1/2, which were further required for hBD-mediated mast cell activation, as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on mast cell degranulation Together, these findings suggest the key role of hBD in inflammatory responses by recruiting and activating mast cells, and increasing vascular permeability

https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.200636379

Antimicrobial peptides human β‐defensin (hBD)‐3 and hBD‐4 activate mast cells and increase skin vascular permeability

Human cathelicidin LL-37 increases vascular permeability in the skin via mast cell activation, and phosphorylates MAP kinases p38 and ERK in mast cells.

Pseudocyst of the auricle is a relatively uncommon condition in which serous fluid accumulates between intracartilaginous space of the ear and manifests as a painless, fluctuant outer ear swelling. Pseudocysts of the auricle have been reported in healthy individuals without clear precipitating or causative factors, with little information on this entity in patients with atopic dermatitis. Here, we describe a case of recurrent pseudocysts of the auricle in a young adult with active facial and ear atopic dermatitis. We also present a specific review of the literature on this condition in patients with atopic dermatitis and discuss a possible association between the two conditions.

Pseudocysts of the auricle in a young adult with facial and ear atopic dermatitis.

In order to assess the safety and efficacy of once-weekly fluconazole orally (100, 150, or 300 mg) with once-a-day topical application of 1% ketoconazole cream in the treatment of onychomycosis in Japan, 121 patients were assigned to one of three fluconazole dosages (100, 150, or 300 mg) and took fluconazole orally, once weekly, for 12 months or until a complete cure was achieved. In addition, once-a-day topical ketoconazole cream was applied. At each weekly visit, adverse events were investigated and the length of the diseased nails was measured. Treatment efficacy was assessed 12 months after discontinuation of fluconazole using the following scale: cured, markedly improved, improved, slightly improved, no change. Mycological cure was assessed using KOH wet mount and fungus culture. The results showed that the numbers of patients achieving marked improvement or better were 38/68 (55%), 13/22 (60%), and 21/31 (67%) for the 100 mg, 150 mg, and 300 mg groups, respectively. There was no significant difference between any two groups. The duration of fluconazole therapy was the longest for patients in the 100 mg group. None of the patients reported adverse effects. These findings led to the conclusion that once-weekly fluconazole with once-a-day application of topical ketoconazole cream appears safe and effective for treating onychomycosis. The dosage of 150 mg once weekly for 6 months was recommended, considering both effectiveness and economy.

Xuejun Chen

Papers

Synergistic effect of antibacterial agents human β-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

Antimicrobial peptides human β‐defensin (hBD)‐3 and hBD‐4 activate mast cells and increase skin vascular permeability

Human cathelicidin LL-37 increases vascular permeability in the skin via mast cell activation, and phosphorylates MAP kinases p38 and ERK in mast cells.

Pseudocysts of the auricle in a young adult with facial and ear atopic dermatitis.

Combination therapy of once-weekly fluconazole (100, 150, or 300 mg) with topical application of ketoconazole cream in the treatment of onychomycosis.