Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes.
The RANTES chemokine is a T cell-expressed, proinflammatory cytokine recently implicated as a suppressive agent of HIV replication. We have identified tandem kappaB-like sequences within the promoter for RANTES that are critical for RANTES promoter-reporter gene activity in both the T cell tumor line Hut78 and in PHA-activated PBL. This region binds not only Rel family members (including p50-p65 heterodimers and p50-p50 homodimers) but also non-Rel factors up-regulated in PBL 3 to 5 days following activation. The expression of these "late" expressed nuclear factors correlates with an up-regulation of RANTES message found at this point in T cell activation. These factors are also constitutively expressed in functionally mature CD8+ T cells. We hypothesize that these apparently novel proteins are responsible in part for the temporal regulation of RANTES seen in peripheral blood T cells and represent a component of transcriptional regulatory machinery newly expressed at this "late" stage of peripheral T cell development.
Nelson
P J
PJ
Clinical Biochemistry Group, Department of Internal Medicine, Clinic Innenstadt, Ludwig Maximilian University of Munich, Munich, Germany.
Ortiz
B D
BD
Pattison
J M
JM
Krensky
A M
AM
D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics*; D004247:DNA; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008745:Methylation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018946:Chemokine CCL5; D004247:DNA; D008156:Luciferases; D003850:Deoxyribonuclease I