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Expression of Enzymes Involved in the Prostanoid Metabolism by Cortical Astrocytes after LPS-induced Inflammation

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Abstract

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.

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Abbreviations

AA:

arachidonic acid

ALOX-5:

5-lipoxygenase

CNS:

central nervous system

COX:

cyclooxygenase

DEX:

dexamethasone

DNA:

deoxyribonucleic acid

EDTA:

ethylenediamine tetraacetic acid

EIA:

enzyme immunosorbent assay

GFAP:

glial fibrillary acidic protein

HPGD:

15-hydroxy prostaglandin dehydrogenase

HPLC:

high-performance liquid chromatography

HPRT:

hypoxanthin-guanin-phosphoribosyl-transferase

IL:

interleukin

LBP:

lipopolysaccharide binding protein

LPS:

lipopolysaccharides

LTB:

leukotrienes

Myd88:

myeloid differentiation factor 88

NS-398:

N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide

OD:

optical density

PCR:

polymerase chain reaction

PG:

prostaglandin

PGDS:

prostaglandin D2 synthase

PGE2 :

prostaglandin E2

PGER:

prostaglandin E2 receptor

PTGES:

prostaglandin E synthase

PTGIS:

prostacyclin synthase

PTGIR:

prostacyclin receptor

PLA2 :

phospholipase A2 (c, cytosolic, i, calcium-dependent, s, secretory)

RNA:

ribonucleic acid

RT:

reverse transcription

SDS:

sodium dodecyl sulfate

TBXAS:

thromboxane-A synthase

TBXs:

thromboxanes

TLR-4:

toll-like receptor 4

TNFα:

tumor necrosis factor α

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Authors and Affiliations

  1. Institute of Neuroanatomy, Medical Clinic, RWTH, Aachen, Germany

    Sonja Johann, Susanne Arnold, Markus Kipp & Cordian Beyer

  2. Institute of Biology II, RWTH, Aachen, Germany

    Eric Kampmann & Jörg Mey

  3. Interdisciplinary Center for Clinical Research (IZKF) “BIOMAT”, RWTH, Aachen, Germany

    Bernd Denecke

  4. Institut für Neuroanatomie, Universitätsklinikum/RWTH Aachen, Wendlingweg 2, 52074, Aachen, Germany

    Cordian Beyer

Authors
  1. Sonja Johann
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  2. Eric Kampmann
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  3. Bernd Denecke
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  4. Susanne Arnold
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  5. Markus Kipp
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  6. Jörg Mey
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  7. Cordian Beyer
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Correspondence to Cordian Beyer.

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Sonja Johann and Eric Kampmann contributed equally.

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Johann, S., Kampmann, E., Denecke, B. et al. Expression of Enzymes Involved in the Prostanoid Metabolism by Cortical Astrocytes after LPS-induced Inflammation. J Mol Neurosci 34, 177–185 (2008). https://doi.org/10.1007/s12031-007-9028-4

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  • DOI: https://doi.org/10.1007/s12031-007-9028-4

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