Differential expression and <i>in vivo</i> secretion of the antimicrobial peptides psoriasin (S100A7), <scp>RN</scp>ase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Wittersheim, Maike; Cordes, Jesko; Meyer‐Hoffert, Ulf; Harder, Jürgen; Hedderich, Jürgen; Gläser, Regine

doi:10.1111/exd.12133

Cited by 39 publications

(46 citation statements)

References 32 publications

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“…This may be because hBD-2 is variably expressed in different regions of the human skin, with the scalp and plantar surfaces having the highest expression, and the perineum, abdomen, and chest expressing a low level of the peptide (Ali et al, 2001). Sex differences in the tinea cruris subgroup, combined group of patients, and controls was unrelated to serum hBD-2 levels (Supplementary Table S3 online), consistent with another report showing that hBD-2 expression is not sexrelated (Wittersheim et al, 2013). Furthermore, age-related changes in hBD-2 expression have been reported, with higher expression being more frequently detected in older individuals (Wittersheim et al, 2013), indicating that the lower hBD-2 level in the tinea cruris subgroup may have been a result of the younger mean age of these patients.…”

Section: Discussionsupporting

confidence: 89%

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Jaradat

Cubillos

Krieg

et al. 2015

Journal of Investigative Dermatology

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Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection.

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Section: Discussionsupporting

confidence: 89%

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Jaradat

Cubillos

Krieg

et al. 2015

Journal of Investigative Dermatology

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“…This inactive precursor consists of an N-terminal cathelin domain and a C-terimal peptide domain. Local proteases, e.g ., serine protease 3, kalikerin-5 or -7, cleave the C-terminal domain from the inactive precursor CAP18 to form active AMP such as LL-37, which is responsible for antimicrobial activity (Table 1) (Glaser et al ., 2005; Radek et al ., 2008; Segaert, 2008; Wittersheim et al ., 2013).…”

Section: Function and Importance Of Key Epidermal Antimicrobial Peptidesmentioning

confidence: 99%

Sphingolipids and Antimicrobial Peptides: Function and Roles in Atopic Dermatitis

Park

Lee

2013

Biomolecules and Therapeutics

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Inflammatory skin diseases such as atopic dermatitis (AD) and rosacea were complicated by barrier abrogation and deficiency in innate immunity. The first defender of epidermal innate immune response is the antimicrobial peptides (AMPs) that exhibit a broad-spectrum antimicrobial activity against multiple pathogens, including Gram-positive and Gram-negative bacteria, viruses, and fungi. The deficiency of these AMPs in the skin of AD fails to protect our body against virulent pathogen infections. In contrast to AD where there is a suppression of AMPs, rosacea is characterized by overexpression of cathelicidin antimicrobial peptide (CAMP), the products of which result in chronic epidermal inflammation. In this regard, AMP generation that is controlled by a key ceramide metabolite S1P-dependent mechanism could be considered as alternate therapeutic approaches to treat these skin disorders, i.e., Increased S1P levels strongly stimulated the CAMP expression which elevated the antimicrobial activity against multiple pathogens resulting the improved AD patient skin.

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“…Human S100 proteins, hBD-2, human beta-defensin 3 (hBD-3), and cathelicidin are significantly higher in fetal keratinocytes than in postnatal skin cells [10]. In addition, psoriasin (S100A7), RNase 7, and hBD-3 are differentially expressed in healthy human skin [11]. When the skin barrier is broken, psoriasin is up-regulated [12].…”

Section: Introductionmentioning

confidence: 99%

Human Antimicrobial Peptides and Proteins

2014

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As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

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Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Cited by 39 publications

References 32 publications

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Low DEFB4 Copy Number and High Systemic hBD-2 and IL-22 Levels Are Associated with Dermatophytosis

Sphingolipids and Antimicrobial Peptides: Function and Roles in Atopic Dermatitis

Human Antimicrobial Peptides and Proteins

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