Expression of enzymes involved in the prostanoid metabolism by cortical astrocytes after LPS-induced inflammation.
Neuroinflammatory processes are a common epiphenomenon for a number of neurological and neurodegenerative diseases. Besides microglia, astrocytes are implicated in brain inflammation in response to harmful stimuli and pathological processes. Bacterial endotoxins can induce the synthesis and release of proinflammatory mediators, i.e., cytokines and chemokines, by astroglia. In this study, we have investigated the effect of lipopolysaccharide (LPS) treatment on the expression of enzymes of prostanoid synthesis and degradation in cultured mouse cortical astrocytes using an Affymetrix Gene Chip array, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and an enzyme-immunosorbent assay. LPS treatment induced an upregulation of enzymes responsible for prostaglandin E2 synthesis, a downregulation of enzymes that catalyzes prostaglandin E2 (PGE2) degradation and production of proinflammatory leukotrienes. Changes in enzyme expression were accompanied by a highly significant increase in extracellular PGE2. Our data demonstrate that astrocytes are directly involved in the complex regulation of proinflammatory prostanoids in the CNS under pathological processes, thus being of potential interest as targets for therapeutical interventions. Further studies are required to unravel the different roles and interactions between astroglia and other cells of the brain-intrinsic innate immune system during inflammation.
Johann
Sonja
S
Institute of Neuroanatomy, Medical Clinic, RWTH, Aachen, Germany.
Kampmann
Eric
E
Denecke
Bernd
B
Arnold
Susanne
S
Kipp
Markus
M
Mey
Jörg
J
Beyer
Cordian
C
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000276:immunology; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone