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
URL:
http://dx.doi.org/10.1007/s004030050037
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