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Activation of astrocyte intracellular signaling pathways by interleukin‐1 in rat primary striatal cultures
Author(s) -
Dunn Sarah L.,
Young Elizabeth A.,
Hall Matthew D.,
McNulty Shaun
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10010
Subject(s) - biology , p38 mitogen activated protein kinases , signal transduction , striatum , microbiology and biotechnology , kinase , phosphorylation , astrocyte , tumor necrosis factor alpha , protein kinase a , endocrinology , central nervous system , dopamine
The striatum has been implicated as the site of action mediating neurotoxic effects of interleukin‐1 (IL‐1) during ischemia. However, the molecular mechanisms underlying these events have yet to be fully addressed. In the present study, primary cultures of rat striatal cells were used as a model for the study of IL‐1 signaling pathways in the striatum. Immunocytochemical analyses revealed that these cultures consisted of a mixture of neurones and astrocytes and demonstrated expression of the IL‐1 type I receptor (IL‐1RI) on both cell types. Treatment with IL‐1 (3 units/ml) for 10 min increased phosphorylation of p38 MAP kinase in striatal cells. The endogenous IL‐1RI inhibitor IL‐1Ra (24 ng/ml) and the p38 MAP kinase inhibitor SB203580 (10 nM) both inhibited this response. Analysis of the effects of IL‐1 on nuclear translocation of the transcription factor NF‐kB revealed that NF‐kB became activated in a time‐dependent manner. Immunocytochemistry revealed that IL‐1 stimulated p38 phosphorylation and NF‐kB translocation in astrocytes only. TaqMan real‐time quantitative PCR analysis revealed that IL‐1 stimulated gene expression of tumor necrosis factor‐α (TNF) in striatal cultures. The p38 MAP kinase inhibitor SB203580 failed to inhibit the effects of IL‐1 on NF‐kB translocation or gene transcription. These studies have demonstrated significant aspects of the IL‐1 signaling cascade in cultured striatum. Of particular interest is the finding that IL‐1 stimulated activation of p38 MAP kinase and NF‐kB in striatal astrocytes exclusively. GLIA 37:31–42, 2002. © 2002 Wiley‐Liss, Inc.