Significance of NF-κB/GATA axis in tumor necrosis factor-α-induced expression of 6-sulfated cell recognition glycans in human T-lymphocytes

Guoyun Chen, Keiichiro Sakuma, Reiji Kannagi

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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-α, 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-κB 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-κB in a transcription factor complex on the 5′-regulatory region of the gene and acts synergistically with NF-κB 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-κB/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.

Original languageEnglish (US)
Pages (from-to)34563-34570
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number50
DOIs
StatePublished - Dec 12 2008
Externally publishedYes

Fingerprint

T-cells
Polysaccharides
Tumor Necrosis Factor-alpha
Cells
Transcription
T-Lymphocytes
Th2 Cells
Nucleic Acid Regulatory Sequences
Leukocytes
Sialic Acid Binding Immunoglobulin-like Lectins
Genes
Sulfotransferases
Selectins
Gene encoding
Chromatin Immunoprecipitation
Cell Adhesion Molecules
N-Acetylneuraminic Acid
Regulator Genes
Helper-Inducer T-Lymphocytes
Immunoprecipitation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Significance of NF-κB/GATA axis in tumor necrosis factor-α-induced expression of 6-sulfated cell recognition glycans in human T-lymphocytes. / Chen, Guoyun; Sakuma, Keiichiro; Kannagi, Reiji.

In: Journal of Biological Chemistry, Vol. 283, No. 50, 12.12.2008, p. 34563-34570.

Research output: Contribution to journalArticle

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