Corticosteroids modulate the binding of recombinant interferons alpha and gamma in Namalva cells.
To investigate possible mechanisms of interaction between corticosteroids and interferons (IFNs), the specific binding of recombinant human IFNs alpha 2 and alpha in Namalva cells after 72 h culture with dexamethasone (10(-8) M to 10(-6) M) was evaluated. Exponentially growing cells were incubated with different concentrations of the radiolabelled IFNs, with or without an excess of unlabelled IFN. The parameters of the interaction between each IFN and its specific receptor were analyzed by the Scatchard method. In the dose range tested, dexamethasone induced a dose-dependent inhibition of Namalva cells growth, which reached about 35% at 10(-6) M. The specific binding of IFN-alpha 2 was decreased to a maximum of 40%, for dexamethasone concentrations greater than or equal to 10(-7) M. The decrease in binding induced by the corticoid was additive with the down-regulation induced by IFN-alpha 2 itself. On the contrary, the specific binding of IFN-alpha was increased by dexamethasone in a dose-dependent fashion within the tested range. The maximal increase in the number of sites per cell was about 60%, with a slight decrease in affinity. These results suggest that complex interactions might arise between corticosteroids and IFNs in the course of their clinical use.
Diez
R A
RA
Unité 196 INSERM, Institut Curie, Section de Biologie, Paris, France.
Mistchenko
A S
AS
Falcoff
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ET
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology*; D007370:Interferon Type I / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000378:metabolism
D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D003907:Dexamethasone; D007371:Interferon-gamma