Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells.
Interleukin-1 (IL-1) and Tumor Necrosis Factor-a (TNFalpha) are potent mediators of inflammatory reactions in the brain. Although much is known about the effects of IL-1 on expression of secretory proteins, few studies have addressed the question of a selective, IL-1-dependent expression of genes involved in neuromodulatory effects of inflammation. Protein-tyrosine-phosphatases (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 applied a DNA-fingerprinting method based on the PCR-amplification of conserved domains of gene families and observed IL-1-dependent induction of two PTP's, cytoplasmic PTPvarepsilon and receptor-PTPgamma, RPTPgamma, in human U373-MG astrocytoma cells. Using Northern blot analysis, we confirmed this result and also show that in addition to IL-1, TNFalpha but not IL-6 induces the transcription of cytoplasmic PTPvarepsilon and RPTPgamma in human astrocytoma cells. Given the important role for PTP's in neuromodulatory aspects such as axonal guidance and neurite outgrowth, cytokine-induced induction of PTP's may play an important pathenogenic role in the development of chronic inflammatory diseases in the brain.
Schumann
G
G
Department of Psychiatry, Albert-Ludwigs Universität, Hauptstrasse 5, 79104, Freiburg, Germany. gunter_schumann@psyallg.ukl.uni-freiburg.de
Fiebich
B L
BL
Menzel
D
D
Hüll
M
M
Butcher
R
R
Nielsen
P
P
Bauer
J
J
D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D016207:Cytokines / Q000494:pharmacology*; D018076:DNA, Complementary / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018076:DNA, Complementary; D007375:Interleukin-1; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C490825:PTPRE protein, human; C516850:PTPRG protein, human; D017027:Protein Tyrosine Phosphatases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5