title: Morphine induced exacerbation of sepsis is mediated by tempering endotoxin tolerance through modulation of miR-146a.
abstract: Development of tolerance to endotoxin prevents sustained hyper inflammation during systemic infections. Here we report for the first time that chronic morphine treatment tempers endotoxin tolerance resulting in persistent inflammation, septicemia and septic shock. Morphine was found to down-regulate endotoxin/LPS induced miR-146a and 155 in macrophages. However, only miR-146a over expression, but not miR-155 abrogates morphine mediated hyper-inflammation. Conversely, antagonizing miR-146a (but not miR-155) heightened the severity of morphine-mediated hyper-inflammation. These results suggest that miR-146a acts as a molecular switch controlling hyper-inflammation in clinical and/or recreational use of morphine.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Santanu
authors.initials: S
authors.lastname: Banerjee
authors.forename: Jingjing
authors.initials: J
authors.lastname: Meng
authors.forename: Subhas
authors.initials: S
authors.lastname: Das
authors.forename: Anitha
authors.initials: A
authors.lastname: Krishnan
authors.forename: Justin
authors.initials: J
authors.lastname: Haworth
authors.forename: Richard
authors.initials: R
authors.lastname: Charboneau
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Sundaram
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: Sabita
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D002460:Cell Line; D004731:Endotoxins / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009020:Morphine / Q000009:adverse effects*; D018805:Sepsis / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D035683:MicroRNAs; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009020:Morphine