title: Control of IL-2 receptor-alpha expression by IL-1, tumor necrosis factor, and IL-2. Complex regulation via elements in the 5' flanking region.
abstract: We have analyzed the mechanisms by which IL-1, IL-2, and TNF regulate expression of IL-2R alpha chain in a rodent T cell line. All three cytokines induce detectable IL-2R alpha mRNA by themselves, but there is strong synergy between IL-1 or TNF, on the one hand, and IL-2, on the other. The earliest phase of induction by IL-1 is independent of protein synthesis. IL-1, but not TNF, also stimulates transient secretion of IL-2. This leads to an autocrine stimulation of a further increase in IL-2R alpha mRNA levels. When IL-2 secretion has dropped off, continued IL-2R alpha expression requires both IL-2 and IL-1. Most or all of this regulation is due to changes in the rate of transcription of the IL-2R alpha gene. The response to IL-1 and IL-2 depends on a segment in the IL-2R alpha 5' flanking region, upstream of all cis-acting regulatory elements previously identified in the human gene.
authors.affiliation: Swiss Institute for Experimental Cancer Research, Genetics Unit, Epalinges, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Plaetinck
authors.forename: M C
authors.initials: MC
authors.lastname: Combe
authors.forename: P
authors.initials: P
authors.lastname: Corthésy
authors.forename: P
authors.initials: P
authors.lastname: Sperisen
authors.forename: H
authors.initials: H
authors.lastname: Kanamori
authors.forename: T
authors.initials: T
authors.lastname: Honjo
authors.forename: M
authors.initials: M
authors.lastname: Nabholz
mesh_terms: D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005809:Genes, Regulator; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase