Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts

Masahiro Oka, Carola Berking, Mark Nesbit, Kapaettu Satyamoorthy, Helmut Schaider, George Murphy, Masamitsu Ichihashi, Edward Sauter, Meenhard Herlyn

    Research output: Contribution to journalArticle

    89 Citations (Scopus)

    Abstract

    Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL- 8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

    Original languageEnglish
    Pages (from-to)595-604
    Number of pages10
    JournalLaboratory Investigation
    Volume80
    Issue number4
    Publication statusPublished - 04-2000

    Fingerprint

    Pyoderma Gangrenosum
    Interleukin-8
    Heterografts
    Ulcer
    Skin
    Neutrophils
    Skin Ulcer
    Severe Combined Immunodeficiency
    Neutrophil Infiltration
    Erythema
    Adenoviridae
    Epidermis
    Fibroblasts
    Erythrocytes
    Cytokines
    Viruses
    Inflammation
    Peptides
    Injections
    DNA

    All Science Journal Classification (ASJC) codes

    • Pathology and Forensic Medicine

    Cite this

    Oka, Masahiro ; Berking, Carola ; Nesbit, Mark ; Satyamoorthy, Kapaettu ; Schaider, Helmut ; Murphy, George ; Ichihashi, Masamitsu ; Sauter, Edward ; Herlyn, Meenhard. / Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. In: Laboratory Investigation. 2000 ; Vol. 80, No. 4. pp. 595-604.
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    abstract = "Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL- 8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.",
    author = "Masahiro Oka and Carola Berking and Mark Nesbit and Kapaettu Satyamoorthy and Helmut Schaider and George Murphy and Masamitsu Ichihashi and Edward Sauter and Meenhard Herlyn",
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    Oka, M, Berking, C, Nesbit, M, Satyamoorthy, K, Schaider, H, Murphy, G, Ichihashi, M, Sauter, E & Herlyn, M 2000, 'Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts', Laboratory Investigation, vol. 80, no. 4, pp. 595-604.

    Interleukin-8 overexpression is present in pyoderma gangrenosum ulcers and leads to ulcer formation in human skin xenografts. / Oka, Masahiro; Berking, Carola; Nesbit, Mark; Satyamoorthy, Kapaettu; Schaider, Helmut; Murphy, George; Ichihashi, Masamitsu; Sauter, Edward; Herlyn, Meenhard.

    In: Laboratory Investigation, Vol. 80, No. 4, 04.2000, p. 595-604.

    Research output: Contribution to journalArticle

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    AU - Oka, Masahiro

    AU - Berking, Carola

    AU - Nesbit, Mark

    AU - Satyamoorthy, Kapaettu

    AU - Schaider, Helmut

    AU - Murphy, George

    AU - Ichihashi, Masamitsu

    AU - Sauter, Edward

    AU - Herlyn, Meenhard

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    N2 - Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL- 8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

    AB - Interleukin-8 (IL-8) is a potent chemotactic polypeptide for neutrophils. However, the role of this cytokine during inflammation remains unclear. Skin specimens from patients with pyoderma gangrenosum demonstrated IL-8 overexpression in skin ulcers, which suggests a role for IL-8 in the development of the disease. We therefore constructed a recombinant adenovirus expressing the complementary deoxyribonucleic acid encoding human IL-8 (IL- 8/Ad5) that induces a 2000-fold increase in IL-8 expression of infected human fibroblasts in vitro. Human skin engrafted to severe combined immunodeficiency mice and then injected with the recombinant virus demonstrated erythema, an intense perivascular infiltration of neutrophils, and extravasation of erythrocytes after 8 hours. By 12 hours after injection, neutrophils had accumulated beneath the epidermis, which then necrotized, and one or more ulcers that remained for approximately 2 weeks were observed. Clinically and histologically, the ulcers resembled pyoderma gangrenosum. These clinical and experimental findings suggest an etiologic role of IL-8 in the pathogenesis of pyoderma gangrenosum.

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