The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology

Takahashi, Toshiya; Gallo, Richard L.

doi:10.1016/j.det.2016.07.006

Cited by 55 publications

(47 citation statements)

References 111 publications

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“…The side-chains of three Cys at positions 3, 4 and 10 in a modified [D-Phe 7 ]-α-MSH [3][4][5][6][7][8][9][10][11][12][13] sequence together with an amino group can form an NS 3 -type chelating structure after appropriate folding of the peptide. As a consequence of the complexation with the radiometal, the initially linear MSH peptide will be cyclized [101].…”

Section: Chelators For Radiometals Used In Melanoma Targetingmentioning

confidence: 99%

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Eberlé

Rout

et al. 2017

CMC

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Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides.

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Section: Chelators For Radiometals Used In Melanoma Targetingmentioning

confidence: 99%

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Eberlé

Rout

et al. 2017

CMC

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“…The skin is an important physical barrier to microorganisms, and skin cells (or other cell types within or around the skin) produce many antimicrobial molecules that contribute to the host defense against bacteria [1]. Most skin antimicrobial peptides, such as β-defensins and cathelicidins, are comprised of approximately 15–20 amino acid residues, and have a net positive charge.…”

Section: Introductionmentioning

confidence: 99%

“…Most skin antimicrobial peptides, such as β-defensins and cathelicidins, are comprised of approximately 15–20 amino acid residues, and have a net positive charge. These peptides interact readily with the negatively charged surface of bacteria, and, in turn, inhibit growth and/or are bactericidal [1, 2]. Individuals with defects in the regulation of these peptides are more susceptible to skin infections [2].…”

Section: Introductionmentioning

confidence: 99%

Neutrophils and Bacterial Immune Evasion

Kobayashi

Małachowa

DeLeo³

2018

J Innate Immun

171

133

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Neutrophils are an important component of the innate immune system and provide a front line of defense against bacterial infection. Although most bacteria are killed readily by neutrophils, some bacterial pathogens have the capacity to circumvent destruction by these host leukocytes. The ability of bacterial pathogens to avoid killing by neutrophils often involves multiple attributes or characteristics, including the production of virulence molecules. These molecules are diverse in composition and function, and collectively have the potential to alter or inhibit neutrophil recruitment, phagocytosis, bactericidal activity, and/or apoptosis. Here, we review the ability of bacteria to target these processes.

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“…showed that keratinocytes from psoriatic skin have increased levels of LL37 and toll‐like receptor (TLR)‐9, and the sequential addition of LL37 and CpG DNA enhanced TLR‐9 responsiveness and type I interferon (IFN) expression. LL37 in the presence of RNA also enhances type I IFN responses in a TLR3‐dependent manner, which may further promote the activation of mDCs . A recent study showed that LL37 was recognized as an autoantigen by circulating T cells in up to 75% of patients with moderate‐to‐severe psoriasis and triggers activation of innate immune cells .…”

Section: Discussionmentioning

confidence: 99%

Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes

Fuentes‐Duculan

Bonifacio

Hawkes

et al. 2017

Experimental Dermatology

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Psoriasis is a common immune-mediated disease that affects 2%-4% of individuals in North America and Europe. In the past decade, advances in research have led to an improved understanding of immune pathways involved in the pathogenesis of psoriasis and has spurred the development of targeted therapeutics. Recently, three psoriasis autoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and lipid antigens generated by phospholipase A2 (PLA2) group IVD (PLA2G4D). It is important to establish the expression, regulation and therapeutic modulation of these psoriasis autoantigens. In this study, we performed immunohistochemistry and two-colour immunofluorescence on non-lesional and lesional psoriasis skin to characterize ADAMTSL5 and LL37, and their co-expression with T cells, dendritic cells, neutrophils and macrophages, which are the main immune cells that drive this disease. Our results showed that ADAMTSL5 and LL37 are significantly (P<.05) increased in lesional skin and are co-expressed by many dendritic cells, macrophages and some T cells in the dermis. Gene expression analysis showed significant (P<.05) upregulation of LL37 in lesional skin and significant downregulation following treatment with etanercept. ADAMTSL5 and LL37 are also significantly decreased by IL-17 or TNF-α blockade, suggesting feed-forward induction of psoriasis autoantigens by disease-related cytokines.

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The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology

Cited by 55 publications

References 111 publications

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Neutrophils and Bacterial Immune Evasion

Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes

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