title: Upregulation by retinoic acid of interleukin-2-receptor mRNA in human T lymphocytes.
abstract: It was previously demonstrated that retinoic acid (RA) can enhance the functional responses of human T lymphocytes by increasing surface IL-2R alpha chain protein expression on proliferating T blasts, resulting in augmented IL-2-dependent growth. In the present study, we used IL-2-maintained lymphoblasts generated from human thymocytes to show that RA enhancement of IL-2R alpha is accompanied by an increase in steady-state levels of IL-2R alpha mRNA. This increase occurred within 1 hr after the addition of RA to the culture and was inhibited by the presence of the protein synthesis inhibitor cycloheximide. RA did not alter the stability of either IL-2R alpha on the cell surface or IL-2R alpha mRNA, suggesting regulation by RA at the level of transcription. This contention was supported by the demonstrated ability of RA to activate the IL-2R alpha promoter in a chloramphenicol acetyltransferase plasmid construct that was transfected into the blast cells. In addition to inducing IL-2R alpha expression, RA also increased the surface expression and mRNA levels of IL-2R beta, the 75-kDa component of the IL-2 receptor that mediates IL-2 signal transduction. These new findings showing regulation by RA of both IL-2R alpha and IL-2R beta suggest multiple pathways by which this retinoid can modulate functional IL-2 receptors.
authors.affiliation: Department of Pathology and Laboratory Medicine, UCLA School of Medicine 90024.
authors.forename: N
authors.initials: N
authors.lastname: Sidell
authors.forename: B
authors.initials: B
authors.lastname: Chang
authors.forename: L
authors.initials: L
authors.lastname: Bhatti
mesh_terms: D002478:Cells, Cultured / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D012313:RNA / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D015375:Receptors, Interleukin-2; D014212:Tretinoin; D012313:RNA; D003513:Cycloheximide