Dexamethasone differentially regulates functional membrane properties in glioma cell lines and primary astrocytes in vitro.
Similar to astrocytes, glioma cells form a well-coupled syncytium via gap junctions. This can be influenced, for example, by activated microglia, the main inflammatory cell population within the central nervous system (CNS). Under pathological conditions such as neoplastic cell growth, microglia number and activation state are enhanced. The aim of the present study is to analyze the influence of dexamethasone (DEX) on cellular and molecular properties in glial coculture models consisting of astroglia and microglia and human and rat glioma cell lines. Primary rat glial cocultures of astrocytes containing 5% (M5, representing "physiological" conditions) or 30% (M30, representing "pathological" conditions) microglia as well as rat and human glioma cell lines (F98, C6, U87) were incubated with DEX for 24 h. DEX-treated M30 cocultures showed significant increased gap junctional intercellular communication (GJIC). DEX treatment of glioma cells resulted in depolarization of the membrane resting potential (MRP) and a significant reduction of GJIC. Furthermore, DEX reduced the amount of activated microglia in M30 cocultures. DEX had no significant effects on the tested variables in the M5 coculture. DEX differentially regulates functional membrane properties of glioma cells and astrocytes in primary glial cocultures, which might resemble steroid effects in glioma cells and adjacent glial components in vivo.
Department of Neurology, Knappschafts Hospital Bochum Langendreer, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany. hinkerohe2@freenet.de
Daniel
D
Hinkerohe
Dörte
D
Wolfkühler
Aiden
A
Haghikia
Carola
C
Meier
Pedro M
PM
Faustmann
Uwe
U
Schlegel
D000818:Animals; D000831:Animals, Newborn; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D018031:Connexin 43 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D053331:Ectodysplasins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000473:pathology / Q000503:physiopathology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D018931:Antineoplastic Agents, Hormonal; D018031:Connexin 43; C506018:EDA protein, human; D053331:Ectodysplasins; D006727:Hormone Antagonists; D015735:Mifepristone; D003907:Dexamethasone