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  • Title: A study of the effect of theophylline on the anti-inflammatory potency of dexamethasone using alpha-aminoisobutyric acid uptake in rat skin fibroblasts: a possible mechanism through the glucocorticoid receptor.
    Author: Xenos K, Kalogeromitros D, Markantonis SL, Katsambas A, Katsarou A.
    Journal: Cell Biol Int; 1998; 22(9-10):695-9. PubMed ID: 10452840.
    Abstract:
    The action of theophylline on the uptake of alpha-aminoisobutyric acid (AIB; an indicator of anti-inflammatory potency) stimulated by the glucocorticoid, dexamethasone, in cultured rat fibroblast monolayers was evaluated. Theophylline alone (0.1 m m) did not show significant activity (3314+/-27 cpm) compared with the baseline level (3186+/-130 cpm), but in the presence of 10 n m dexamethasone the stimulation of AIB uptake was increased to 5263+/-100 cpm, approximately to the same extent as with 100 n m dexamethasone alone (5397+/-28 cpm). Activation of glucocorticoid-receptor complexes in rat fibroblast cytosol was studied by assessing the extent of their binding to DNA-cellulose. Activated and non-activated forms of glucocorticoid-receptor complexes were analysed by DEAE-Sephadex chromatography. Theophylline (1 m m) was found to have a direct effect (0 degrees C), similar to that of heat (25 degrees C) on DNA-cellulose binding, that is approximately 64.5% and 68.7%, respectively, thus indicating that theophylline promotes activation of glucocorticoid receptors at low temperature. The effect of theophylline on the stimulation of AIB uptake by dexamethasone when considered in the light of its activation of GR receptors in the fibroblast cytosol indicates that this effect may be mediated by GR activation.
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