Significance of NF-kappaB/GATA axis in tumor necrosis factor-alpha-induced expression of 6-sulfated cell recognition glycans in human T-lymphocytes.
Sulfated glycans play critical roles in various cell recognition events among leukocytes. The 6-sulfated lactosamine glycans in particular have been widely noted for their importance because they are involved in cell recognition events mediated by cell-adhesion molecules such as selectins and sialic acid-recognizing molecules such as siglecs and also in the activation of CD44 in binding to extracellular matrix hyaluronate. A pro-inflammatory cytokine, tumor necrosis factor-alpha, induces expression of 6-sulfated glycans on human leukocytes. Here we report that the transcription of the GlcNAc6ST-1 gene, the gene encoding a sulfotransferase for 6-sulfated glycan synthesis, is induced in human T-lymphoid cells through tandem NF-kappaB and GATA motifs in its 5'-regulatory region. Results of our reporter assays, immunoprecipitation, and chromatin immunoprecipitation analyses indicated that GATA-3 and/or GATA-2, but not GATA-1, associates with NF-kappaB in a transcription factor complex on the 5'-regulatory region of the gene and acts synergistically with NF-kappaB in triggering GlcNAc6ST-1 transcription. Recently, a skin-homing subset of helper memory T cells exhibiting the Th2 marker CCR4 was shown to specifically express 6-sulfated glycans. The transactivation mechanism described here suggested that GlcNAc6ST-1 transcription is coordinated with the NF-kappaB/GATA-3 axis, which is known to figure heavily in Th2 cell differentiation. In line with this, in vitro differentiation of human T cells to Th2 cells was found to significantly induce GlcNAc6ST-1 transcription and 6-sulfated glycan expression.
Department of Molecular Pathology, Aichi Cancer Center, Nagoya 464-8681, Japan.
Guo-Yun
GY
Chen
Keiichiro
K
Sakuma
Reiji
R
Kannagi
D001483:Base Sequence; D002454:Cell Differentiation; D050989:GATA2 Transcription Factor / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000737:chemistry; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry*; D054398:Receptors, CCR4 / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D016328:NF-kappa B; D011134:Polysaccharides; D054398:Receptors, CCR4; D015238:Sulfotransferases; D014409:Tumor Necrosis Factor-alpha; D000097811:Carbohydrate Sulfotransferases; C515354:CCR4 protein, human; C494711:GATA2 protein, human; C494749:GATA3 protein, human