title: MiR-146b Mediates Endotoxin Tolerance in Human Phagocytes.
abstract: A proper regulation of the innate immune response is fundamental to keep the immune system in check and avoid a chronic status of inflammation. As they act as negative modulators of TLR signaling pathways, miRNAs have been recently involved in the control of the inflammatory response. However, their role in the context of endotoxin tolerance is just beginning to be explored. We here show that miR-146b is upregulated in human monocytes tolerized by LPS, IL-10, or TGFβ priming and demonstrate that its transcription is driven by STAT3 and RUNX3, key factors downstream of IL-10 and TGFβ signaling. Our study also found that IFNγ, known to revert LPS tolerant state, inhibits miR-146b expression. Finally, we provide evidence that miR-146b levels have a profound effect on the tolerant state, thus candidating miR-146b as a molecular mediator of endotoxin tolerance.
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy ; Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy.
authors.forename: Tiziana Ada
authors.initials: TA
authors.lastname: Renzi
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy ; Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Rubino
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy ; Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gornati
authors.affiliation: Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy ; Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy ; Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Italy ; Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Graziella
authors.initials: G
authors.lastname: Curtale
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D047468:Immunoprecipitation; D016753:Interleukin-10 / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D004731:Endotoxins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D016753:Interleukin-10