Abstract
Several skin sensitizers, like 2,4-dinitrofluorobenzene (DNFB), are known to provoke contact hypersensitivity responses after topical application. Here, we show that DNFB can upregulate macrophage inflammatory protein-2 (MIP-2) expression in RAW 264.7 cells via a mechanism that is largely dependent on mitogen-activated protein kinase (MAPK) signaling pathways. ELISA-based transcription factor activation assays and chromatin immunoprecipitation assays revealed that functional interaction between AP-1 and MIP-2 promoter element is necessary for MIP-2 gene expression by DNFB. Interestingly, topical application of DNFB to NC/Nga mice increased MIP-2 expression in dermis, suggesting that MIP-2 contributes to the leukocyte infiltration associated with atopic dermatitis. These results provide additional insight of the mechanism of contact hypersensitivity induced by contact sensitizers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Topical
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Animals
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Cell Line
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Chemokine CXCL2 / genetics*
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Chemokine CXCL2 / metabolism
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Chemotaxis, Leukocyte / genetics
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Dermatitis, Atopic / chemically induced
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Dermatitis, Atopic / genetics
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Dermis / drug effects
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Dermis / metabolism
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Dinitrofluorobenzene / administration & dosage
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Dinitrofluorobenzene / adverse effects
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Dinitrofluorobenzene / pharmacology*
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Enzyme Activation / physiology
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Gene Expression Regulation / drug effects*
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Male
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Promoter Regions, Genetic / drug effects
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Protein Binding / drug effects
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Proto-Oncogene Proteins c-jun / metabolism
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Specific Pathogen-Free Organisms
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Chemokine CXCL2
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Proto-Oncogene Proteins c-jun
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Dinitrofluorobenzene
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases