Abstract
Munro's microabscesses contain polymorphonuclear leukocytes and form specifically in the epidermis of psoriasis patients. The mechanism whereby the neutrophils are recruited into the epidermis is poorly understood. Using a combination of human and mouse primary keratinocyte cell cultures and the imiquimod-induced psoriasis-like mouse model of skin inflammation, we explored the role of IL-1 signaling in microabscess formation. In vitro imiquimod stimulated production of IL-1α and neutrophil recruiting chemokines. Imiquimod-activated chemokine expression was dependent upon adenosine signaling and independent of IL-1α and IL-1 receptor type 1 (IL-1R1); nevertheless, IL-1α could enhance chemokine expression initiated by imiquimod. Topical application of imiquimod in vivo led to epidermal microabscess formation, acanthosis, and increased IL-1α and chemokine expression in the skin of wild-type mice. However, in IL-1R1-deficient mice these responses were either absent or dramatically reduced. These results demonstrate that IL-1α and IL-1R1 signaling is essential for microabscess formation, neutrophil recruiting chemokine expression, and acanthosis in psoriasis-like skin inflammation induced by imiquimod.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Abscess / chemically induced*
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Abscess / immunology
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Abscess / pathology
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Adjuvants, Immunologic / pharmacology
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Aminoquinolines / pharmacology*
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Animals
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Animals, Newborn
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Chemokine CXCL1 / immunology
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Chemokine CXCL1 / metabolism
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Chemokine CXCL2 / immunology
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Chemokine CXCL2 / metabolism
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Dermis / cytology
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Drug Eruptions / immunology*
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Drug Eruptions / pathology
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Epidermal Cells
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Humans
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Imiquimod
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Interleukin-1alpha / immunology
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Interleukin-1alpha / metabolism
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Keratinocytes / cytology
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Keratinocytes / immunology*
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Keratinocytes / metabolism
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Mice
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Mice, Knockout
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Neutrophils / cytology
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Neutrophils / immunology
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Neutrophils / metabolism
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Primary Cell Culture
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Psoriasis / chemically induced
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Psoriasis / immunology
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Psoriasis / pathology
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Receptors, Interleukin-1 Type I / genetics
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Receptors, Interleukin-1 Type I / immunology*
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Receptors, Interleukin-1 Type I / metabolism*
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Signal Transduction / immunology
Substances
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Adjuvants, Immunologic
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Aminoquinolines
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Chemokine CXCL1
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Chemokine CXCL2
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Cxcl1 protein, mouse
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Cxcl2 protein, mouse
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Interleukin-1alpha
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Interleukin-1beta
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Receptors, Interleukin-1 Type I
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Imiquimod