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Tumor Necrosis Factor-α Up-Regulates the Expression of β1,4-Galactosyltransferase-I in Human Fibroblast-like Synoviocytes

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Abstract

β1,4-Galactosyltransferase-I (β1,4-GalT-I), which transfers galactose to the terminal N-acetylglucosamine of N- and O-linked glycans in a β1,4-linkage, is considered to be the major galactosyltransferase among the seven members of the subfamily responsible for β4 galactosylation. We previously reported, for the first time, that β1,4-GalT-I may play an important role in the inflammatory processes in synovial tissue of patients with rheumatoid arthritis (RA). In this study, we analyzed whether β1,4-GalT-I expression correlates with the expression of tumor necrosis factor-α (TNF-α) in RA. We show firstly the overexpression and co-localization of β1,4-GalT-I and TNF-α in synovial tissue of RA patients. Then, lipopolysaccharide (LPS) induces β1,4-GalT-I mRNA up-regulation in fibroblast-like synoviocytes (FLSs) through endogenous TNF-α overexpression. In addition, we observed that not only endogenous TNF-α but also exogenous TNF-α induced β1,4-GalT-I mRNA production in FLSs, and TNF-α-knockdown reverses the up-regulation of β1,4-GalT-I in FLSs induced by LPS or TNF-α. These results suggest that TNF-α contributes to the up-regulation of β1,4-GalT-I mRNA in human FLSs.

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ACKNOWLEDGMENTS

This work was supported by the National Natural Scientific Foundation of China Grant (No. 30770488, No. 31070723, and No. 81070275), Natural Scientific Foundation of Jiangsu Province Grant (No. BK2006547), College and University Natural Scientific Research Programme of Jiangsu Province (No. 03KJB180109), and “Ke-Jiao-Xing-Wei-Zhong-Dian-Yi-Xue-Ren-Cai” Financial Assistance of Jiangsu Province (RC2007087).

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Xu, D., Cui, Z., Liu, W. et al. Tumor Necrosis Factor-α Up-Regulates the Expression of β1,4-Galactosyltransferase-I in Human Fibroblast-like Synoviocytes. Inflammation 34, 531–538 (2011). https://doi.org/10.1007/s10753-010-9260-x

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