title: Transcription regulates HIF-1α expression in CD4(+) T cells.
abstract: The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates the metabolic adaptation of cells to hypoxia and T-helper cell fate. However, HIF-1α regulation in CD4(+) T cells (T cells) remains elusive. Here we observed that depletion of oxygen (O2⩽2%) alone was not sufficient to induce HIF-1α expression in T cells. However, when hypoxic T cells were stimulated, HIF-1α was expressed and this was dependent on nuclear factor-κB- and nuclear factor of activated T cell (NFAT)-mediated transcriptional upregulation of Hif-1α mRNA. HIF-1α upregulation could be blocked by drugs inhibiting NF-κB, NFAT or mammalian target of rapamycin precluding CD4(+) T-cell stimulation or translation in T cells, as well as by blocking transcription. CD3, CD28, phorbol-12-myristat-13-acetat (PMA) or ionomycin-stimulated T cells did not express HIF-1α under normoxic conditions. In conclusion, regulation of HIF-1α expression in CD4(+) T cells in hypoxia gravely relies on its transcriptional upregulation and subsequent enhanced protein stabilization.
authors.affiliation: Department of Molecular Biology, Sciences III, University of Geneva, Geneva, Switzerland.|Department of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bollinger
authors.affiliation: Division of Immunology and Allergy, Department of Medical Specialties, University Hospital and Medical Faculty, Geneva, Switzerland.
authors.forename: Annalena
authors.initials: A
authors.lastname: Bollinger
authors.affiliation: Department of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.|Department of Molecular and Clinical Infectious Diseases, University of Lübeck, Lübeck, Germany.
authors.forename: Sydney
authors.initials: S
authors.lastname: Gies
authors.affiliation: Department of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.|Department of Molecular and Clinical Infectious Diseases, University of Lübeck, Lübeck, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Feldhoff
authors.affiliation: Department of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Solbach
authors.affiliation: Department of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.|Department of Molecular and Clinical Infectious Diseases, University of Lübeck, Lübeck, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger