Xylosyltransferase-1 Expression Is Refractory to Inhibition by the Inflammatory Cytokines Tumor Necrosis Factor α and IL-1β in Nucleus Pulposus Cells

• DOI: 10.1016/j.ajpath.2014.09.021
• Publication Date: 2014-12-02T04:05:36Z
• Authors: Wei Ye; Jie Zhou; Dessislava Z. Mar...; Ye Tian; Jun Li; D. Greg Anderson; Irving M. Shapiro; Makarand V. Risbud
• Keywords: Refractory (planetary science)

We investigated whether expression of xylosyltransferase-1 (XT-1), a key enzyme in glycosaminoglycan biosynthesis, is responsive to disk degeneration and inhibition by the inflammatory cytokines tumor necrosis factor α IL-1β nucleus pulposus (NP) cells. Analysis human NP tissues showed that XT-1 unaffected severity; Jun, Fos, Sp1 mRNA were positively correlated. Cytokines failed inhibit promoter activity expression. However, decreased promoters containing deletion mutation -730/-723 bp AP-1 motif, prompting us investigate role Sp1/Sp3 regulation healthy Overexpression suppression modulated activity. Likewise, treatment with inhibitors WP631 mithramycin A or cotransfection plasmid DN-Sp1 Inhibitors stable knockdown Sp3 resulted Genomic chromatin immunoprecipitation analysis binding motifs located at -684/-677 -227/-217 -124/-114 promoter. These results suggest refractory disease process signaling through AP-1, Sp1, important maintenance levels