Cyclosporin A inhibits the interleukin 2 receptor alpha chain gene transcription but not its cell surface expression: the alpha chain stability can explain this discrepancy.
The effect of the immunosuppressor cyclosporin A (CsA) on the expression of interleukin (IL) 2 receptors was investigated in a human T cell line IARC301 which constitutively expresses such receptors. This cell line also spontaneously secretes IL2 which supports its autocrine growth. We have previously shown that CsA prevents the constitutive transcription of the IL2 gene in these cells. Here we show that as soon as 4 h after CsA addition, the transcription of the gene encoding the alpha chain (p55) of IL2R was inhibited. IL2 can transiently increase the expression of this gene. CsA did not prevent this transient IL2-dependent induction of IL2R alpha, but could still partially inhibit it. Once IL2 induction was over, CsA exerted its full inhibition. Thus, CsA does not seem to inhibit IL 2R alpha gene transcription simply by inhibition of IL2 synthesis. However, no modification of IL2R alpha expression on the cell surface could be detected after 48 h in the presence of CsA. This discrepancy between the effect of CsA on IL2R alpha expression as probed at the mRNA or the protein level can be accounted for by the stability of the IL2R alpha protein after synthesis. Indeed, the half-life of IL2R alpha chain is longer than 40 h. This suggests that the alpha chain, after it is endocytosed together with the beta chain as a component of high-affinity IL2R, might recycle back to the cell surface.
Hémar
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A
Département d'Immunologie, Institut Pasteur, Paris, France.
Dautry-Varsat
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A
D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D003524:Cyclosporins; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2