Expression and regulation of interleukin-10 and interleukin-10 receptor in rat astroglial and microglial cells

Annemarie Ledeboer, John J P Brevé, Anne Wierinckx, Saskia van der Jagt, Adrian F Bristow, Josée E Leysen, Fred J H Tilders, Anne-Marie Van Dam

Research output: Contribution to journalArticleAcademicpeer-review

158 Citations (Scopus)


Activated glial cells crucially contribute to brain inflammatory responses. Interleukin-10 (IL-10) is an important modulator of glial cell responses in the brain. In the present study we describe the expression of IL-10 and the IL-10 receptor (IL-10R1) in primary cocultures of rat microglial and astroglial cells. Using quantitative RT-PCR and ELISA, we show that IL-10 mRNA expression and subsequent IL-10 secretion is time-dependently induced by lipopolysaccharide (LPS). IL-10R1, however, is constitutively expressed in glial cell cocultures, as shown by RT-PCR and immunocytochemistry. Radioligand binding studies using 125I-IL-10 reveal that rat glial cells express a single binding site with an apparent affinity of approximately 600 pm for human IL-10. Observations in enriched cultures of either microglial or astroglial cells indicate that both cell types express IL-10 mRNA and are capable of secreting IL-10. Both cell types also express IL-10R1 mRNA and protein. However, in glial cell cocultures immunoreactive IL-10R1 protein is predominantly observed in astrocytes, suggesting that microglial expression of IL-10R1 in cocultures is suppressed by astrocytes. In addition, exogenous IL-10 is highly potent in down-regulating LPS-induced IL-1beta and IL-10 mRNA, and, at a higher dose, IL-10R1 mRNA in untreated and LPS-treated cultures, suggesting that IL-10 autoregulates its expression and inhibits that of IL-1beta at the transcriptional level. Together the findings support the concept that IL-10, produced by activated microglial and astroglial cells, modulates glia-mediated inflammatory responses through high-affinity IL-10 receptors via paracrine and autocrine interactions.

Original languageEnglish
Pages (from-to)1175-85
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number7
Publication statusPublished - Oct 2002


  • Animals
  • Animals, Newborn
  • Astrocytes
  • COS Cells
  • Cells, Cultured
  • Coculture Techniques
  • Comparative Study
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-1
  • Interleukin-10
  • Journal Article
  • Lipopolysaccharides
  • Microglia
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Research Support, Non-U.S. Gov't
  • Transcription, Genetic
  • Transfection

Cite this