IL-6 secreted by astroglial cells regulates Na-K-Cl cotransport in brain microvessel endothelial cells

Dandan Sun, Christian Lytle, Martha E O'Donnell

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


We showed previously that cerebral microvessel endothelial cells (CMEC) exhibit a prominent Na-K-Cl cotransporter that functions to regulate intracellular volume and may also mediate vectorial ion transport across the blood-brain barrier (BBB). Astrocytes and their conditioned media induce BBB properties of the endothelium. Our previous studies demonstrated that exposure of CMEC to astroglial cells markedly increases cotransport activity, upregulates cotransporter protein expression, and also increases cotransporter protein phosphorylation. In the present study, we evaluated the possibility that astroglial effects on the Na-K-Cl cotransporter are mediated by astroglial cell-secreted interleukin-6 (IL-6). Cotransporter activity was assessed as bumetanide-sensitive K influx, and protein expression was evaluated by Western blot analysis. Exposing CMEC to IL-6 for 48 h caused a dose-dependent stimulation of Na-K-Cl cotransport activity. Both C6 glial cell-conditioned medium (C 6CM)-induced and IL-6-induced increases in cotransport activity were neutralized by anti-IL-6 antibodies. A 48-h exposure of cells to IL-6 or C 6CM also resulted in increased cotransporter protein expression. Furthermore, using an enzyme-baked immunosorbent assay for IL-6, we found significant amounts of IL-6 in C 6CM. These data suggest that astroglia-secreted IL-6 may mediate the observed astroglial cell effects on CMEC Na-K-Cl cotransport and further support the hypothesis that astrocytes participate in maintenance of cerebral ionic homeostasis by regulating Na-K-Cl cotransporter function at the BBB.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6 41-6
StatePublished - 1997


  • Blood-brain barrier
  • Bumetanide
  • Cultured cerebral microvessel endothelial cells
  • Cytokines
  • Primary astrocytes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)


Dive into the research topics of 'IL-6 secreted by astroglial cells regulates Na-K-Cl cotransport in brain microvessel endothelial cells'. Together they form a unique fingerprint.

Cite this