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Uhlmann, S., Mannsperger, H., Zhang, J.D., Horvat, E.A., Schmidt, C., Kublbeck, M., Henjes, F., Ward, A., Tschulena, U., Zweig, K., Korf, U., Wiemann, S. and Sahin, O. (2012) Global MicroRNA Level Regulation of EGFR-Driven Cell-Cycle Protein Network in Breast Cancer. Molecular Systems Biology, 8, 570. http://dx.doi.org/10.1038/msb.2011.100

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• TITLE: IL-10 Inhibits LPS-Induced Expression of miR-147 in Murine Macrophages

  AUTHORS: Leah N. Cardwell, Brian K. Weaver

  KEYWORDS: IL-10, Lipopolysaccharide, Macrophage, Inflammation, MicroRNA

  JOURNAL NAME: Advances in Biological Chemistry, Vol.4 No.4, June 26, 2014

  ABSTRACT: Interleukin-10 (IL-10) mediates an anti-inflammatory response that constrains immune responses and limits inflammation-associated pathology. IL-10 does so, in part, by selectively inhibiting pro-inflammatory cytokine and chemokine expression induced in macrophages in response to Toll-like receptor (TLR) signaling. The IL-10-mediated anti-inflammatory response is executed through the activation of STAT3 leading to induction of target genes referred to as IL-10-induced genes. As miRNAs have emerged as important negative regulators of gene expression in various systems, we sought to address whether the IL-10-mediated anti-inflammatory response acts through regulated expression of miRNA genes. Using quantitative PCR-based arrays, we examined 140 miRNA genes with putative roles in inflammation for changes in expression in response to IL-10 and lipopoly-saccharide (LPS) in primary mouse macrophages. IL-10 stimulation resulted in the inhibition of miR-147 expression induced in response to LPS, while having a potentiating effect on the induction of miR-455. miR-147 is the second TLR-induced miRNA, in addition to miR-155, identified to be counter-regulated by IL-10. Its suppression by IL-10 suggests that miR-147 may have an unknown pro-inflammatory function in TLR-triggered macrophages. The results extend the notion that IL-10 selectively regulates expression of miRNA genes, and that miRNA-mediated pathways are a component of the IL-10-mediated anti-inflammatory response.