Research: Cell Migration

EpubMeares et al. Regulation of CCL20 expression in astrocytes by IL-6 and IL-17.Glia. 2012 Feb

Astrocytes have an important role in the regulation of inflammation within the central nervous system (CNS). In neuroinflammatory conditions such as multiple sclerosis, numerous cytokines and chemokine are elevated including interleukin 6 (IL-6), interleukin 17 (IL-17), and Macrophage Inflammatory Protein-3 (CCL20). IL-17 enhances IL-6 signaling and subsequent IL-6 expression in astrocytes. CCL20 is a chemokine that functions as a chemoattractant to facilitate the recruitment of CCR6 (CCL20 receptor-expressing cells, including Th17 cells (a type of T cell that is thought to cause autoimmunity). In this study, we examined the role of IL-6 and IL-17 on CCL20 production in primary mouse astrocytes. IL-6 in combination with the soluble interleukin 6 receptors (the receptor is cleaved from its anchorage in the cell) stimulated CCL20 expression in part through STAT3 activation, whereas IL-17 alone had no effect. However, the combination of IL-6, sIL-6R, and IL-17 led to a robust increase in CCL20 production. IL-17 increased the activation-associated phosphorylation of NF-κB, and inhibition of the NF-κB pathway significantly inhibited the enhancement of CCL20 expression by IL-17. In addition, chromatin immunoprecipitation revealed that stimulation of primary astrocytes with IL-6 plus the sIL-6R induced STAT3 binding to the CCL20 promoter. Combined stimulation with IL-6, sIL-6R, and IL-17 increased the recruitment of phosphorylated NF-κB to the CCL20 promoter (the bit that promotes the gene to be activated to make the CCL20 protein) and other things consistent with a transcriptionally active gene. The astrocyte-produced CCL20 increased T cell migration as determined by transwell migration assay. Collectively, these results suggest that astrocytes, in response to IL-6, sIL-6R, and IL-17, may shift chemokine production to that favoring T cell recruitment to the CNS.Early this week we reported evidence of the same cascade occurred to promote Th17 white blood cell migration into the CNS. This is what this study is reporting. That is not surprising as you are often not the only one to have a bright idea. So two scientists can do things at the same time, unaware of the other. However whilst they agree on the process, they do not agree on the cell type involved, one implies it comes from cells in the blood vessel the other an astrocyte. Could they both be right..maybe, could one be wrong…maybe. Astrocytes are inimately associated with blood vessels of the brain. Is this the answer..who knows. This is a good example how things can differ in the literature, we need someone else to come in with their view. Eventually weight of evidence occcurs to indicate the most likely answer. This type of debate is occurring in other aspects of MS all the time….Disagreement is part of the research process.

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