Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins

Harder, Jürgen; Schröder, Jens‐Michael

doi:10.1189/jlb.0704409

Cited by 203 publications

(169 citation statements)

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“…The fractions were obtained by application of psoriatic scales to heparin-affinity columns to enrich for cationic peptides, followed by separation with C8 RP-HPLC [10]. By using this approach, we identified four fractions with the ability to induce type I IFN production in pDCs, eluting after 22, 23, 24, and 26 min (Fig.…”

Section: Psoriatic Skin Fractions Containing Hbd2 Hbd3 and Lysozymementioning

confidence: 99%

“…Another key feature of psoriasis is the excessive production of antimicrobial peptides (AMPs) and proteins by keratinocytes [10][11][12]. These AMPs are best known for their role in killing pathogenic microorganisms such as Gram-positive and Gramnegative bacteria, protozoa, fungi, as well as some viruses [13].…”

Section: Introductionmentioning

confidence: 99%

“…Here, these T cells produce Th17 cytokines 7], which directly initiate keratinocyte proliferation and an abnormal epidermal differentiation pattern [8,9]. Another key feature of psoriasis is the excessive production of antimicrobial peptides (AMPs) and proteins by keratinocytes [10][11][12]. These AMPs are best known for their role in killing pathogenic microorganisms such as Gram-positive and Gramnegative bacteria, protozoa, fungi, as well as some viruses [13].…”

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confidence: 99%

“…Cathelicidins are a family of alpha-helical peptides containing LL37 as the only human member [14,15], β-defensins a family of beta-sheet peptides containing human beta-defensin (hBD)1, hBD2 [16], and hBD3 [17], and S100 proteins containing S100A7 (psoriasin) that is abundantly expressed in psoriatic skin [18,19]. Other AMPs overexpressed in psoriatic skin include RNase7, elafin, lysozyme, and neutrophil gelatinase associated lipocalin [10].The strong expression of AMPs in psoriasis skin has been classically linked to the inability of a psoriatic plaque to be infected [20]. Recently, this AMP overexpression was also linked to the aberrant activation of pDC to produce IFN and the pathogenesis of psoriasis [21].…”

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confidence: 99%

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Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self‐DNA

et al. 2014

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Psoriasis is a T-cell-mediated skin autoimmune disease characterized by the aberrant activation of dermal dendritic cells (DCs) and the sustained epidermal expression of antimicrobial peptides. We have previously identified a link between these two events by showing that the cathelicidin antimicrobial peptide LL37 has the ability to trigger selfnucleic acid mediated activation of plasmacytoid DCs (pDCs) in psoriatic skin. Whether other cationic antimicrobial peptides exert similar activities is unknown. By analyzing heparin-binding HPLC fractions of psoriatic scales, we found that human beta-defensin (hBD)2, hBD3, and lysozyme are additional triggers of pDC activation in psoriatic skin lesions. Like LL37, hBD2, hBD3, and lysozyme are able to condense self-DNA into particles that are endocytosed by pDCs, leading to activation of TLR9. In contrast, other antimicrobial peptides expressed in psoriatic skin including elafin, hBD1, and psoriasin (S100A7) did not show similar activities. hBD2, hBD3, and lysozyme were detected in psoriatic skin lesions in the vicinity of pDCs and found to cooperate with LL37 to induce high levels of IFN production by pDCs, suggesting their concerted role in the pathogenesis of psoriasis.Keywords: Antimicrobial peptides r Plasmacytoid DC r Psoriasis r Skin r Toll-like receptor Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPsoriasis is a common T-cell-mediated inflammatory disease of the skin, which, in its most prevalent form, is characterized by the appearance of scaly erythematous plaques that may cover large Correspondence: Dr. Michel Gilliet e-mail: Michel.gilliet@chuv.ch areas of the patient's body [1][2][3]. A key feature of psoriasis is the abnormal activation of dendritic cell (DC) subsets in the dermal compartment leading to the downstream T-cell-mediated autoimmune cascade [4]. A role for plasmacytoid DCs (pDCs) producing type I IFNs appears to be central in this process. pDC-derived * These authors contributed equally to this work.www.eji-journal.eu 204Roberto Lande et al. Eur. J. Immunol. 2015. 45: 203-213 IFNs activate conventional DCs that stimulate autoimmune T cells to migrate into the epidermis [5]. Here, these T cells produce Th17 cytokines 7], which directly initiate keratinocyte proliferation and an abnormal epidermal differentiation pattern [8,9]. Another key feature of psoriasis is the excessive production of antimicrobial peptides (AMPs) and proteins by keratinocytes [10][11][12]. These AMPs are best known for their role in killing pathogenic microorganisms such as Gram-positive and Gramnegative bacteria, protozoa, fungi, as well as some viruses [13]. The antimicrobial activity of AMPs has been ascribed to their unique cationic and amphiphatic structure, which allows interaction with and disruption of microbial membranes containing a high degree of negative charges. Three major antimicrobial peptide classes found in psoriatic skin are the cathelicidin, β-defensins, or S100 proteins. ...

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Section: Psoriatic Skin Fractions Containing Hbd2 Hbd3 and Lysozymementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self‐DNA

et al. 2014

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“…Crohn's disease [1][2][3], atopic dermatitis [3,4], Kostmann's disease [5], and cystic fibrosis [6,7] are linked to microbial infections due to decreased expression of anti-microbial peptides in these patients. By contrast, the anti-microbial peptides are highly expressed in the lesions of psoriasis, resulting in fewer microbial infections [3,8,9]. Furthermore, knockout mice lacking CRAMP or β-defensin-1 are highly susceptible to bacterial infections [10,11].…”

Section: Introductionmentioning

confidence: 99%

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

Komatsuzawa

Ouhara

Yamada

et al. 2005

The Journal of Pathology

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The innate immune system is the primary defence against bacterial infection. Among the factors involved in innate defence, anti-microbial peptides produced by humans have recently attracted attention due to their relevance to some diseases and also to the development of new chemotherapeutic agents. Staphylococcus aureus is one of the major human pathogens, causing a variety of infections from suppurative disease to food poisoning. Methicillin-resistant S. aureus (MRSA) is a clinical problem and with the recent emergence of a vancomycin-resistant strain, this will pose serious problems in the near future. In investigating the molecular biology of S. aureus infections to develop new chemotherapeutic agents against MRSA infections, knowledge of the interaction of innate anti-microbial peptides with S. aureus is important. In vitro and in vivo experiments demonstrate that exposure of S. aureus to host cells can induce the anti-microbial peptides β-defensin-2 (hBD2), hBD3, and LL37/CAP18. The induction level of these peptides differs among strains, as does the susceptibility of the strains, with MRSA strains exhibiting lower susceptibility. In summary, the susceptibility of S. aureus strains, including MRSA strains, to components of the innate immune system varies, with the MRSA strains showing more resistance to both innate immune factors and chemotherapeutic agents.

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Skin: Immunological Defence Mechanisms

Nickoloff

2013

Encyclopedia of Life Sciences

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Human skin is the largest organ of the body providing a protective coat to ensure that exogenous ‘noxious’ agents do not jeopardise the function of vital internal organ systems. Being situated at the interface between external and internal milieus, a number of remarkable structural and functional characteristics of skin have been delineated that contribute to its effectiveness at maintaining homoeostasis. For instance, skin is normally healthy despite the fact that it is regularly colonised by a variety of organisms. Antimicrobial peptides secreted by skin cells contribute to this homoeostatic maintenance of microorganisms by forming a shield against infectious agents. Several immune cell types are also resident in the skin and are ready to respond to a variety of stimuli. Balancing the multiple skin defensive mechanisms is important for achieving homoeostasis as disruption of any of these components contribute to the manifestation of skin diseases. Key Concepts: Normal skin consists of multiple cell types – some that form the different layers and others that function as sentinels of the immune system. Skin is colonised by a variety of microorganisms under homoeostatic conditions. Skin has multiple innate defence mechanisms that are disrupted during dermatological diseases. Adaptive immunity in the skin is shaped by the response of different dendritic cells and T‐cells that are ready to respond to different stimuli. AMPs are natural antibiotics that are present in the skin to prevent overgrowth of microorganisms. Dysregulated production of AMPs is associated with a variety of dermatological diseases.

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Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins

Cited by 203 publications

References 100 publications

Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self‐DNA

Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self‐DNA

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

Skin: Immunological Defence Mechanisms

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