CONSTITUTIVE AND CYTOKINE-INDUCIBLE EXPRESSION OF PRION PROTEIN GENE IN HUMAN NEURAL CELL-LINES

Prion diseases are a group of neurodegenerative disorders characterize d by intracerebral accumulation of a protease-resistant prion protein (PrPSc) that causes extensive neuronal degeneration and astrogliosis. The regulation of prion protein (PrP) gene expression by a panel of gl ial and neuronal cytokines (TNF-alpha, IFN-gamma?I, IL-1 beta, IL-IO, and TGF-beta 1) was investigated in human neural cell lines by reverse transcription-polymerase chain reaction and Northern blot analysis. T he constitutive expression of PrP mRNA was identified in all human neu ral cell lines and tissues examined including Y79 retinoblastoma, IMR- 32 neuroblastoma, SK-N-SH neuroblastoma, U-373MG astrocytoma, KG-I-C g lioma, NTera2 teratocarcinoma, NTera2-derived differentiated neurons ( NTera2-N), peripheral nerve, and cerebral and cerebellar tissues. In S K-N-SH cells, a 48 hour (h) treatment with 100 ng/ml IL-1 beta, 100 ng /ml TNF-alpha, or 100 nM phorbol 12-myristate 13-acetate induced a 2.7 - to 4.2-fold increase in the level of PrP mRNA, while the exposure to 100 ng/ml IFN-gamma resulted in a 50% decrease. By contrast, none of these cytokines significantly altered the levels of PrP mRNA in IMR-32 , NTera2-N, or U-373MG cells. These results indicate that the PrP gene expression is constitutive in a wide range of human neural cell lines and tissues where it is controlled by cell type-specific regulatory m echanisms.