CONSTITUTIVE AND CYTOKINE-REGULATED EXPRESSION OF PRESENILIN-1 AND PRESENILIN-2 GENES IN HUMAN NEURAL CELL LINES

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To investigate the role of pleiotropic neuronal and glial cytokines in the regulation of presenilin (PS) gene expression in human neural cells, both presenilin-1 (PS1) and presenilin-2 (PS2) mRNA levels were analyzed by Northern blotting in SK-N-SH neuroblastoma, IMR-32 neuroblastoma, NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), and U-373MG astrocytoma cells following exposure to proinflammatory cytokines (TNF-α, IFN-γ, or IL-1β), anti -inflammatory cytokines (IL-10 or TGF-β1), dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate (PMA). The constitutive expression of PS1 (3.0 kb) and PS2 (2.3 kb) mRNA was identified in all these cell lines, in which PS1 mRNA levels were unaltered following treatment with any cytokines and factors examined. By contrast, PS2 mRNA expression was up-regulated substantially in SK-N-SH cells by exposure to TNF-α and in U-373MG cells by treatment with IFN-γ, whereas it was down-regulated in both NTera2-N and U-373MG cells following exposure to IL-1βor PMA. The levels of PS2 mRNA remained unchanged in IMR-32 cells after these treatment. These results indicate that PS1 and PS2 genes are expressed constitutively in a panel of human neural cell lines where PS2 mRNA expression is affected by a distinct set of cytokines via cell type-specific mechanisms that do not alter PS1 mRNA levels, suggesting the existence of separated regulatory systems controlling the expression of PS1 and PS2 genes in human neural cells.