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Interleukin‐1 increases expression of cytosolic and membrane PGE synthase in mouse astrocytes and brain
Author(s) -
O'Banion M. K.,
Maida M. E.,
Moore A. H.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.3_16.x
Subject(s) - cytosol , atp synthase , gene isoform , prostaglandin e , cyclooxygenase , astrocyte , biology , prostaglandin , chemistry , microbiology and biotechnology , medicine , endocrinology , biochemistry , enzyme , central nervous system , gene
Increased production of prostaglandin E 2 (PGE 2 ) accompanies inflammatory responses, both peripherally and in the brain. Previous studies have demonstrated marked up‐regulation of cyclooxygenase‐2 (COX‐2) expression by IL‐1β in mouse astrocytes and brain. However, selective increases in PGE 2 production are dependent on expression of downstream PGE synthases. Therefore, we have investigated regulation of two PGE synthase isoforms in cultured murine astrocytes and in mouse brain treated with IL‐1β. In astrocytes exposed to 10 ng/mL IL‐1β we see an early and dramatic increase in cytosolic PGE synthase mRNA and protein expression at 4 and 8 h that largely subsides by 24 h. This pattern is similar to that observed for COX‐2 expression. Interestingly, increases in membrane PGE synthase levels also occur, but with a delayed time course. Similar increases in both isoforms are observed following intraparenchymal injection of 5 ng recombinant IL‐1β. More specifically, the in vivo increase in COX‐2 mRNA was accompanied by an increase in membrane PGE synthase mRNA levels 6 h following IL‐1β injection. Subsequently, protein expression of both the cytosolic and membrane PGE synthases was elevated at 24 h. Interestingly, administration of NS‐398, a COX‐2 specific inhibitor, attenuated IL‐1β‐induced changes in PGE synthase expression, suggesting regulation of these isoforms by a COX‐2‐dependent mechanism. Together these data suggest that up‐regulation of both PGE synthase isoforms contributes to cerebral inflammatory responses to IL‐1β. Acknowledgements: Supported by RO1 NS33553 to MKO.