Significance of NF-κB/GATA Axis in Tumor Necrosis Factor-α-induced Expression of 6-Sulfated Cell Recognition Glycans in Human T-lymphocytes
Significance of NF-κB/GATA Axis in Tumor Necrosis Factor-α-induced Expression of 6-Sulfated Cell Recognition Glycans in Human T-lymphocytes
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DOI：
10.1074/jbc.m804271200
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发表时间：
2008-12-12
影响因子：
4.8
通讯作者：
Kannagi, Reiji
中科院分区：
文献类型：
--
作者：
Chen, Guo-Yun;Sakuma, Keiichiro;Kannagi, Reiji
硫酸化聚糖在白细胞中的各种细胞识别事件中起关键作用。特别地，6-硫酸化乳糖胺聚糖因其重要性而被广泛注意，因为它们参与由细胞粘附分子如选择素和唾液酸识别分子如siglecs介导的细胞识别事件，并且还参与CD 44与细胞外基质透明质酸盐结合的活化。促炎细胞因子肿瘤坏死因子-α诱导人白细胞上6-硫酸聚糖的表达。在这里，我们报告了GlcNAc 6ST-1基因的转录，该基因编码6-硫酸化聚糖合成的磺基转移酶，在人T淋巴细胞中通过其5 '调控区的串联NF-κ B和加塔基序诱导。我们的报告基因分析、免疫沉淀和染色质免疫沉淀分析的结果表明，加塔-3和/或加塔-2（而非加塔-1）与NF-κ B在基因5 '调控区的转录因子复合物中结合，并与NF-κ B协同作用触发GlcNAc 6ST-1转录。最近，显示Th 2标记物CCR 4的辅助记忆T细胞的皮肤归巢亚群显示特异性表达6-硫酸化聚糖。本文所述的反式激活机制表明GlcNAc 6ST-1转录与NF-κ B/加塔-3轴协调，已知NF-κ B/GATA-3轴在Th 2细胞分化中起重要作用。与此一致，发现人T细胞向Th 2细胞的体外分化显著诱导GlcNAc 6ST-1转录和6-硫酸化聚糖表达。
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-kappa B 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-kappa B in a transcription factor complex on the 5'-regulatory region of the gene and acts synergistically with NF-kappa B 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-kappa B/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.