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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 288 (1996), S. 147-152 
    ISSN: 1432-069X
    Keywords: Key words Phospholipases A ; Epidermal inflammation ; Keratinocytes ; Cytokines ; Corticosteroids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phospholipase A 2 (PLA 2 )-catalysed liberation of arachidonic acid is the rate-limiting step in the generation of the lipid mediators prostaglandins and leukotrienes. PLA 2 regulation thus represents a pivotal mechanism in the pathogenesis of inflammation. In this study we investigated the effects of TNFα and IL-1α on PLA 2 activity in cultured murine keratinocytes. Starting 18 h after stimulation, PLA 2 activity increased significantly by about 250–320%) in the supernatants and in the cell pellets. This effect was completely inhibited either by preincubation of the cells with dexamethasone 48 h before stimulation or by coincubation with actinomycin D. PLA 2 acitivty detected in the supernatants was blocked by reduction with dithiothreitol, whereas the PLA 2 activity in the pellets was dithiothreitol-resistant. We conclude that in murine keratinocytes IL-1α induce de novo synthesis and release of a secretory PLA 2 and the induction of a different PLA 2 activity in the cytosol. These findings indicate a crucial link betweeen early cytokine effects and the initiation of the lipid mediator cascade in keratinocytes. The observation that PLA 2 induction could be completely inhibited by preincubation with dexamethasone allows new insights into the mechanism of steroid effects on epidermal inflammation and renders PLA 2 regulation an interesting therapeutic target.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 289 (1997), S. 194-203 
    ISSN: 1432-069X
    Keywords: Key words HMC-1 cell line ; Extracellular matrix ; protein ; Integrin ; c-kit ; Cadherin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Skin mast cells are typically located in the perivascular or perineural connective tissue. We observed that HMC-1 mast cells growing in suspension adhered efficiently to (〉 90% of cells) and spread on top of fibroblast monolayers and to a lesser degree on purified extracellular matrix proteins. Since adhesive interactions determine cell migration and tissue localization we studied the mechanism. It was found that HMC-1 cells attach to collagen I and fibronectin, laminin, collagen IV and vitronectin, but not to collagens III and VI or hyaluronic acid. Adhesion to fibronectin, collagen I and laminin was completely inhibited by mAbs blocking β 1 -integrins, whereas adhesion of HMC-1 cells to vitronectin was inhibited by anti-α v -chain mAbs. However, attachment of HMC-1 cells to fibroblasts was not influenced by mAbs blocking β 1 - or α v -chain function, by RGD peptides or by mAbs interfering with other receptors, most notably c- kit . Identical results were obtained with normal mast cells isolated from human foreskin. These results indicate that human mast cells attach to fibroblasts independently of β 1 - or α v -integrins as well as of c- kit receptor-mediated mechanisms. The functional characteristics observed (i.e. only partial sensitivity to trypsin and EDTA, no increase in trypsin sensitivity by pretreatment with EDTA) suggest that cadherin receptors were not involved, and it is likely that the adhesion process observed involved not-yet-defined heterotypic cell-cell adhesion receptors.
    Type of Medium: Electronic Resource
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