β-1,4-galactosyltransferase I promotes tumor necrosis factor-α autocrine via the activation of MAP kinase signal pathways in Schwann cells.

Recent studies have demonstrated that aberrant galactosylation is associated with some inflammation diseases. β-1,4-Galactosyltransferase-I (β-1,4-GalT I), which transferred galactose to the terminal N-acetylglucosamine of N- and O-linked glycans in a β-1,4-linkage, was considered to be the major galactosyltransferase among the seven members of the subfamily responsible for β4 galactosylation. To elucidate the expression and possible function of β-1,4-GalT I in the peripheral nervous system (PNS) inflammatory diseases, we performed a tumor necrosis factor-alpha (TNF-α) autocrine inflammatory model in Schwann cells (SCs). In this study, we found that silencing of β-1,4-GalT I suppressed TNF-α autocrine, while overexpression of β-1,4-GalT I promoted TNF-α autocrine in TNF-α-treated SCs. Meanwhile, anti-TNFR1 antibody suppressed the expression of β-1,4-GalT I, and TNF-α autocrine. β-1,4-GalT I conferred its effect by promoting ERK, JNK, and P38 MAP kinase signal pathways activation in TNF-α-induced SCs. Thus, the present data shows that during SCs activation, β-1,4-GalT I may play an important role in the release of inflammatory mediators.