Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported previously that in vitro treatment of human blood derived dendritic cells (DC) with contact allergens provokes the elevated expression of mRNA for interleukin (IL) 1beta, under conditions where similar treatment of cells with the non-sensitizing skin irritant sodium lauryl sulfate (SLS) did not alter IL-1beta mRNA levels (Reutter et al., 1997). The purpose of the present investigation was to evaluate further this phenomenon and to explore the potential utility of this approach for the purpose of skin sensitization testing. Human peripheral blood progenitor cells prepared from healthy adult volunteers were cultured in the presence of IL-4 and granulocyte/macrophage colony stimulating factor. After 5 days of culture, the majority of cells had a Langerhans cell-like phenotype, with characteristic dendritic morphology and cell surface expression of CD83, major histocompatibility complex class II and CD1a determinants. These blood-derived DC were cultured in the presence of the contact allergen 2,4-dinitrofluorobenzene (DNFB), SLS or vehicle alone and mRNA expression for IL-1beta, IL-6 and IL-18 was analysed by semiquantitative reverse transcriptase polymerase chain reaction. Constitutive expression of all three cytokines was observed for DC isolated from all donors examined. Exposure to DNFB resulted in upregulation of IL-1beta mRNA (two- to threefold) in cells derived from three out of eight donors whereas IL-6 and IL-18 were largely unaffected by allergen exposure. In contrast, SLS treatment did not induce IL-1beta mRNA expression in any of the donors investigated. Analysis of cytokine mRNA expression using the protocol described by Reutter et al. (1997), did not increase the sensitivity of measurement of induced cytokine expression. Although selected upregulation of IL-1beta by blood derived DC has been confirmed, a wider range of contact allergens and irritants need to be assessed before this approach could be considered for hazard identification.
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PMID:Investigation of induced changes in interleukin 1beta mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. 1090 42

Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following skin sensitization. However, the cytokine signals that control these responses following skin irritation have yet to be defined. We demonstrate that IL-1alpha, a cytokine associated with skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in skin-draining lymph nodes. Stimulation of these responses by IL-1alpha required the local availability of TNF-alpha. Using specific neutralizing antibodies, LC migration induced following skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1beta and independent of a requirement for IL-1alpha. However, the converse was true following stimulation of responses with the nonsensitizing skin irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1alpha and not IL-1beta. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-alpha but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms.
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PMID:Differential regulation of epidermal langerhans cell migration by interleukins (IL)-1alpha and IL-1beta during irritant- and allergen-induced cutaneous immune responses. 1214 Jan 76