CYTOKINE-INDUCED TRANSCRIPTION OF PROTEIN-TYROSINE-PHOSPHATASES IN HUMAN ASTROCYTOMA-CELLS

Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF alpha) an po tent mediators of inflammatory reactions in the brain. Although much i s known about the effects of IL-1 on expression of secretory proteins, few studies have addressed the question of a selective, IL-1-dependen t expression of genes involved in neuromodulatory effects of inflammat ion. Protein-tyrosine-phosphstases (PTP's) have been shown to regulate signal transduction and adhesion processes in the developing nervous system. They are candidates for inflammation-induced neuromodulation. Therefore, we investigated if IL-1 regulates expression of PTP's. We a pplied a DNA-fingerprinting method based on the PCR-amplification of c onserved domains of gene families and observed IL-1-dependent inductio n of two PTP's, cytoplasmic PTP epsilon and receptor-PTP gamma, RPTP g amma, in human U373-MG astrocytoma cells. Using Northern blot analysis , we confirmed this result and also show that in addition to IL-1, TNF alpha but not IL-6 induces the transcription of cytoplasmic PTP epsil on and RTP gamma in human astrocytoma cells. Given the important role for PTP's in neuromodulatory aspects such as axonal guidance and neuri te outgrowth, cytokine-induced induction of PTP's may play an importan t pathenogenic role in the development of chronic inflammatory disease s in the brain. (C) 1998 Elsevier Science B.V. All rights reserved.