Abstract
Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Apoptosis / radiation effects*
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Candida albicans / immunology
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Candidiasis / drug therapy
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Candidiasis / immunology
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Candidiasis / pathology
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Combined Modality Therapy / methods
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Female
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Ficusin / pharmacology
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Humans
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Hypersensitivity, Delayed / drug therapy
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Hypersensitivity, Delayed / immunology
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Hypersensitivity, Delayed / pathology
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Immune Tolerance / drug effects*
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Immune Tolerance / immunology
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Immune Tolerance / radiation effects*
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Immunosuppression Therapy / methods
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Inflammation / drug therapy
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Inflammation / immunology
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Inflammation / pathology
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Interleukin-10 / immunology
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Lymphoma, T-Cell, Cutaneous / drug therapy
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Lymphoma, T-Cell, Cutaneous / immunology
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Lymphoma, T-Cell, Cutaneous / pathology
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Male
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Mice
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Mice, Knockout
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PUVA Therapy* / adverse effects
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PUVA Therapy* / methods
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Platelet Activating Factor / immunology*
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Platelet Membrane Glycoproteins / deficiency
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Platelet Membrane Glycoproteins / immunology
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Psoriasis / drug therapy
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Psoriasis / immunology
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Psoriasis / pathology
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Receptors, G-Protein-Coupled / deficiency
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Receptors, G-Protein-Coupled / immunology
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Signal Transduction / radiation effects
Substances
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Platelet Activating Factor
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Platelet Membrane Glycoproteins
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Receptors, G-Protein-Coupled
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platelet activating factor receptor
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Interleukin-10
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Ficusin