Induction and Localization of Cutaneous Interleukin-1 Beta mRNA During Contact Sensitization
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2000/12/15
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Description:Chemical allergens that induce contact sensitivity cause changes in levels of epidermal cytokines, In mice one of the earliest epidermal cytokines to be upregulated following sensitization is interleukin-1 beta (IL-1 beta), The present study investigated the kinetics and in situ localization of induced IL-1 beta expression in mouse skin following topical exposure to the contact allergen oxazolone. Mice were exposed topically to 1% oxazolone, with control mice exposed to vehicle (acetone:olive oil 4:1) alone, and at various times thereafter skin was excised for IL-1 beta mRNA and protein determination by in situ hybridization and enzyme-linked immunosorbant assay (ELISA), respectively. IL-1 beta mRNA was found to be expressed constitutively at low levels in skin from naive (untreated) and vehicle-treated mice, with mRNA localized in some hair follicles and sebaceous glands; no IL-1 beta mRNA was detected in the epidermis of control animals. Following topical exposure of mice to oxazolone for 5-15 min, upregulation of IL-1 beta mRNA was observed in the epidermis, dermis, hair follicles, and sebaceous glands; at 90 min and beyond the pattern of IL-1 beta mRNA expression declined toward control. Analysis of whole skin homogenates by ELISA demonstrated cutaneous IL-1 beta protein to be present constitutively in both vehicle-treated and naive mice. Following exposure to oxazolone, cutaneous IL-1 beta protein expression was elevated at 30 min, decreased at 1 h, and fell below the limit of detection of the assay at 2 h before returning to constitutive levels at 4 and 24 h. IL-1 beta protein levels in vehicle-treated mice, naive mice, and mice treated with the respiratory allergen trimellitic anhydride were unchanged over this time period. The present study demonstrated that IL-1 beta mRNA expression was upregulated rapidly and transiently in well-defined regions of mouse epidermis and dermis during contact sensitization, and was succeeded by an elevation in IL-1 beta protein. This early highly localized upregulation of IL-1 beta lends further support to the hypothesis that this cytokine plays a key role in the initial stages of skin sensitization. Such information will enhance our understanding of the molecular processes involved in allergic contact dermatitis and may provide a mechanistic basis for designing refined animal and in vitro alternatives to existing models of skin sensitization. [Description provided by NIOSH]
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ISSN:0041-008X
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Pages in Document:231-237
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Volume:169
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Issue:3
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NIOSHTIC Number:nn:20032179
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Citation:Toxicol Appl Pharmacol 2000 Dec; 169(3):231-237
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Contact Point Address:F. Kermani, Univ London Imperial Coll Sci Technol & Med, Sir Alexander Fleming Bldg, London SW7 2AZ, England
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Federal Fiscal Year:2001
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Peer Reviewed:True
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Source Full Name:Toxicology and Applied Pharmacology
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Main Document Checksum:urn:sha-512:e6bd7e6630cdd9af3cb6979fc260d16dfedd345178b51e06c5339081a1081b3d71335a2e72f3a4090e14caee25852c2818fc2a85f3c173e52ee668e5c1b608e6
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