Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis
Staphylococcal infections of the skin are more common in patients with atopic dermatitis than they are in normal persons or patients with psoriasis. In this study, the investigators hypothesized that the elevated rate of skin infections in atopic dermatitis could be attributed to reduced levels of t...
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| Published in | The New England journal of medicine Vol. 347; no. 15; pp. 1151 - 1160 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Boston, MA
Massachusetts Medical Society
10.10.2002
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Staphylococcal infections of the skin are more common in patients with atopic dermatitis than they are in normal persons or patients with psoriasis. In this study, the investigators hypothesized that the elevated rate of skin infections in atopic dermatitis could be attributed to reduced levels of the endogenous antimicrobial peptides LL-37 and human β-defensin 2. They found that the levels of these peptides were lower in skin from patients with atopic dermatitis.
The skin's first line of defense against invasion by microbial agents is the stratum corneum, a nonviable, desiccated layer of the epidermis.
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However, this physical barrier is susceptible to injuries that allow the entry of opportunistic microbial agents into the skin. The innate immune system can immediately respond to this intrusion by helping to prevent further invasion. This immune response includes phagocytosis by neutrophils and macrophages and their production of reactive oxygen intermediates that kill microbial agents.
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A number of endogenous antimicrobial peptides have been shown to play an integral part in innate immunity.
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Two major classes of peptides in . . . |
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| AbstractList | Staphylococcal infections of the skin are more common in patients with atopic dermatitis than they are in normal persons or patients with psoriasis. In this study, the investigators hypothesized that the elevated rate of skin infections in atopic dermatitis could be attributed to reduced levels of the endogenous antimicrobial peptides LL-37 and human β-defensin 2. They found that the levels of these peptides were lower in skin from patients with atopic dermatitis.
The skin's first line of defense against invasion by microbial agents is the stratum corneum, a nonviable, desiccated layer of the epidermis.
1
However, this physical barrier is susceptible to injuries that allow the entry of opportunistic microbial agents into the skin. The innate immune system can immediately respond to this intrusion by helping to prevent further invasion. This immune response includes phagocytosis by neutrophils and macrophages and their production of reactive oxygen intermediates that kill microbial agents.
2
A number of endogenous antimicrobial peptides have been shown to play an integral part in innate immunity.
3
Two major classes of peptides in . . . The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human beta-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis.BACKGROUNDThe innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human beta-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis.The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay.METHODSThe expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay.Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Real-time RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus.RESULTSImmunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Real-time RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus.A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus.CONCLUSIONSA deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus. Background The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and β-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human β-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis. Methods The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay. Results Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Real-time RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus . Conclusions A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus . The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human beta-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis. The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay. Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Real-time RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus. A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus. The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta -defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human beta -defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis. The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay. Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Realtime RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus. A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus. |
| Author | Ohtake, Takaaki Ganz, Tomas Ong, Peck Y Boguniewicz, Mark Brandt, Corinne Leung, Donald Y.M Strickland, Ian Gallo, Richard L |
| Author_xml | – sequence: 1 givenname: Peck Y surname: Ong fullname: Ong, Peck Y – sequence: 2 givenname: Takaaki surname: Ohtake fullname: Ohtake, Takaaki – sequence: 3 givenname: Corinne surname: Brandt fullname: Brandt, Corinne – sequence: 4 givenname: Ian surname: Strickland fullname: Strickland, Ian – sequence: 5 givenname: Mark surname: Boguniewicz fullname: Boguniewicz, Mark – sequence: 6 givenname: Tomas surname: Ganz fullname: Ganz, Tomas – sequence: 7 givenname: Richard L surname: Gallo fullname: Gallo, Richard L – sequence: 8 givenname: Donald Y.M surname: Leung fullname: Leung, Donald Y.M |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13978812$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/12374875$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2002 Massachusetts Medical Society. All rights reserved. 2002 INIST-CNRS Copyright 2002 Massachusetts Medical Society |
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| Keywords | Human Immunohistochemistry Measurement Allergy Immunopathology Skin disease Peptides Psoriasis Activity Exploration Antimicrobial agent Atopy Infection Pathology Endogenous Atopic dermatitis Skin Molecular biology Reverse transcription polymerase chain reaction Comparative study Immune system |
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| Snippet | Staphylococcal infections of the skin are more common in patients with atopic dermatitis than they are in normal persons or patients with psoriasis. In this... The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta-defensins. In normal skin these peptides are... Background The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and β-defensins. In normal skin these peptides... The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta -defensins. In normal skin these peptides are... |
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| SubjectTerms | Adult Allergic diseases Antimicrobial agents Antimicrobial Cationic Peptides - genetics Antimicrobial Cationic Peptides - metabolism Antimicrobial Cationic Peptides - pharmacology Bacterial infections beta-Defensins - genetics beta-Defensins - metabolism beta-Defensins - pharmacology Biological and medical sciences Cathelicidins Cell Line Dermatitis Dermatitis, Atopic - immunology Dermatology Gene Expression - drug effects Gene Expression Regulation Humans Immune system Immunoblotting Immunopathology Keratinocytes - cytology Keratinocytes - immunology Keratinocytes - metabolism Medical sciences Peptides Psoriasis Psoriasis - immunology Psoriasis. Parapsoriasis. Lichen RNA, Messenger - genetics RNA, Messenger - metabolism Skin - immunology Skin - pathology Skin allergic diseases. Stinging insect allergies Staphylococcus aureus - drug effects Tumor Necrosis Factor-alpha - pharmacology Viral infections |
| Title | Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis |
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