title: Induction and localization of cutaneous interleukin-1 beta mRNA during contact sensitization.
abstract: 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 (Iota L-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 naïve (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 naïve 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, naïve 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.
authors.affiliation: Molecular Toxicology, Imperial College School of Medicine, Sir Alexander Fleming Building, London SW7 2AZ, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Kermani
authors.forename: M S
authors.initials: MS
authors.lastname: Flint
authors.forename: S A
authors.initials: SA
authors.lastname: Hotchkiss
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis*; D012867:Skin / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D010081:Oxazolone