Significance of NF-κB/GATA Axis in Tumor Necrosis Factor-α-induced Expression of 6-Sulfated Cell Recognition Glycans in Human T-lymphocytes

Abstract

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 celladhesion 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-␣, 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-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-B in a transcription factor complex on the 5-regulatory region of the gene and acts synergistically with NF-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-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.

Clarithromycin Inhibits Type A Seasonal Influenza Virus Infection in Human Airway Epithelial Cells

“…Clarithromycin also reduced NF-B proteins induced by influenza virus infection. These findings are consistent with those reported previously (Delmotte et al, 2002;Suzuki et al, 2002;Yasukawa et al, 2005;Chen et al, 2008). Clarithromycin might reduce the expression of SA␣2,6Gal on the cells partly through the reduction of NF-B activation.…”

“…However, tumor necrosis factor-␣, one of inflammatory mediators in airways, increases the expression glycosyltransferase and sulfotransferase responsible for biosynthesis of sialylated epitopes in the bronchial mucosa (Delmotte et al, 2002), through the activation of NF-B (Chen et al, 2008). ␣2,6-Sialic acid in glycoproteins also increases in inflamed mouse serum in response to turpentine oil (Yasukawa et al, 2005).…”

c-Myb, Menin, GATA-3, and MLL form a dynamic transcription complex that plays a pivotal role in human T helper type 2 cell development

“…38,39 In another example, nuclear factor-B (NF-B) is known to be activated by T-cell receptor engagement, and activation of important downstream target genes, such as GlNAc6ST-1, a gene that encodes a sulfotransferase required for the synthesis of 6-sulfated cell recognition glycans, is dependent on physical interaction with GATA-3. 40 Das et al have also shown that in NF-B p50-deficient mice, CD4 ϩ T cells failed to induce GATA-3 expression under Th2 priming condition but maintained unimpaired T-bet and IFN-␥ expression under Th1 differentiation conditions. 41 These reports initially suggested the possibility that a c-Myb/GATA-3 coactivator complex might include Smad3 or NF-B.…”

Manduca sexta moricin promoter elements can increase promoter activities of Drosophila melanogaster antimicrobial peptide genes

“…Adjacent κB and GATA sites have been identified in many insect immune gene promoters and both sites are required for gene induction (Harshman and James, 1998; Kadalayil et al, 1997; Senger et al, 2004; Tingvall et al, 2001). Human GATA-3 and/or GATA-2 interact with NF-κB to trigger GlcNac6ST-1 transcription (Chen et al, 2008). In addition, κB and GATA sites are both required for induced expression of Drosophila cecropin A (Kadalayil et al, 1997).…”