Characterization of the promoter of human CRTh2, a prostaglandin D2 receptor.
Chemoattractant-receptor homologous molecule expressed on Th2 cells (CRTh2) is a receptor for prostaglandin (PG)D2, a lipid mediator involved in allergic inflammation. CRTh2 is expressed by Th2 cells, eosinophils and basophils and PDG(2)-CRTh2 signaling induces calcium mobilization, cell migration and expression of the Th2 cytokines IL-4, IL-5, and IL-13. Despite the role of CRTh2 in allergic inflammation, transcriptional regulation of this gene has not been studied. Here, we demonstrated that a reporter construct of the CRTh2 promoter was induced following T cell stimulation. This activity could be further enhanced by over-expression of GATA-3, but not NFAT2 or STAT6. Electromobility shift assay demonstrated GATA-3 binding to a probe from the CRTh2 promoter. This study provides the first detailed analysis of transcriptional regulation of the human CRTh2 promoter. These findings may help identify strategies to attenuate expression of this gene and influence the maintenance and proliferation of Th2 cells in allergic inflammation.
Quapp
Russell
R
Department of Medicine, Division of Pulmonary Medicine, Pulmonary Research Group, 574B Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada T6G 2S2.
Madsen
Norman
N
Cameron
Lisa
L
D000818:Animals; D003198:Computer Simulation; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D050990:GATA3 Transcription Factor; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C036293:prostaglandin D2 receptor