Context-dependent IL-6 potentiation of interferon- gamma-induced IL-12 secretion and CD40 expression in murine microglia

Hsiao Wen Lin, Steven W. Levison

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Interleukin-6 (IL-6) is produced by neurons, astrocytes, and microglia, and elevated levels of IL-6 within the CNS have been documented in multiple neurological disorders including Alzheimer's disease, stroke, epilepsy, attention deficit disorder, cerebral palsy, and multiple sclerosis. Here, we sought to understand how IL-6 regulates microglial signal transduction and their immune properties. Using highly enriched cultures of neonatal murine microglia we show that IL-6 alone has direct effects on microglia as it activates STAT3 and extracellular signal-regulated kinase pathways in a time- and dose-dependent fashion and it enhances interferon-gamma (IFNγ)-stimulated IL-12 secretion. However, other immune properties were only weakly modulated by IL-6 when administered without the soluble IL-6 receptor (sIL-6R). For instance, IFNγ-induced expression of the co-stimulatory molecule, CD40 was dependent on sIL-6R administration. IL-6 with or without sIL-6R did not affect major histocompatability complex class II expression. In granulocyte-macrophage colony-stimulating factor (GMCSF)-induced dendritic cell-like microglia, IL-6/sIL-6R and IFNγ stimulated an even greater increase in CD40 expression compared with primary microglia. Altogether, our results demonstrate that microglial responses to IL-6 are not simple in that the effects of IL-6 are context-dependent. In particular, the presence or absence of sIL-6R, IFNγ or GMCSF will alter the type and amplitude of their response.

Original languageEnglish (US)
Pages (from-to)808-818
Number of pages11
JournalJournal of neurochemistry
Volume111
Issue number3
DOIs
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • CNS
  • Co-stimulatory molecules
  • Granulocyte-macrophage colony-stimulating factor
  • Inflammation
  • Soluble interleukin-6 receptors

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