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

Autor: Ledeboer, Annemarie, Brevé, John J P, Wierinckx, Anne, van der Jagt, Saskia, Bristow, Adrian F, Leysen, Josée E, Tilders, Fred J H, Van Dam, Anne-Marie
Přispěvatelé: Anatomy and neurosciences, Radiology and nuclear medicine, Clinical pharmacology and pharmacy, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Neurodegeneration
Jazyk: angličtina
Rok vydání: 2002
Zdroj: Ledeboer, A, Brevé, J J P, Wierinckx, A, van der Jagt, S, Bristow, A F, Leysen, J E, Tilders, F J H & Van Dam, A-M 2002, ' Expression and regulation of interleukin-10 and interleukin-10 receptor in rat astroglial and microglial cells ', European Journal of Neuroscience, vol. 16, no. 7, pp. 1175-85 .
European Journal of Neuroscience, 16(7), 1175-85. Blackwell Publishing Ltd Oxford, UK
ISSN: 0953-816X
Popis: 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.
Databáze: OpenAIRE
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