title: Inhibition of astrocyte TNFalpha expression by extracellular potassium.
abstract: TNFalpha and IL-6 are cytokines of great interest, given the numerous biological activities and the documented expression in several central nervous system (CNS) pathologies. In this report, we have examined cultures of IL-1- or IL-1/IFNgamma-activated human fetal astrocytes as a model to study mechanisms of cytokine regulation in the inflamed CNS. Since one of the major functions of astrocytes is spatial buffering of K(+) ions, we examined the effect of high extracellular KCl on astrocyte cytokine expression by ribonuclease protection assay and ELISA. Results demonstrate that astrocyte TNFalpha production was potently inhibited by K(+) with 44 and 89% inhibition at 25 and 55 mM K+, respectively. In contrast, astrocyte IL-6 inhibition required higher concentrations of K+ (>/=75 mM). These results demonstrate a novel role for astrocyte potassium channel activity in modulation of glial cytokine production.
authors.affiliation: Department of Pathology (F-717), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: H Y
authors.initials: HY
authors.lastname: Chang
authors.forename: L L
authors.initials: LL
authors.lastname: Hua
authors.forename: A
authors.initials: A
authors.lastname: Morgan
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
mesh_terms: D001253:Astrocytes / Q000166:cytology* / Q000276:immunology*; D002478:Cells, Cultured; D005110:Extracellular Space; D005333:Fetus / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006947:Hyperkalemia / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D009573:Nitrites / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D009573:Nitrites; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011189:Potassium Chloride; D007371:Interferon-gamma