title: Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice.
abstract: BACKGROUND
  The natural polyphenolic compound curcumin has been proved to modulate innate immune responses and possess anti-inflammatory properties. Nevertheless, the mechanism remains poorly understood, particularly regarding curcumin-regulated miRNAs under inflammatory response.
  
  
  OBJECTIVE
  This study investigates the role of miRNA-155 in the effects of curcumin on inflammatory response in cell and a mouse model.
  
  
  METHODS
  The anti-inflammatory activity of curcumin (5, 10 and 15 μM, 2 h) in lipopolysaccharide (LPS, 200 ng/mL)-induced cells were measured by quantitative PCR. The animals were treated orally by 20 mg/kg curcumin for 3 days before an LPS intraperitoneal injection (10 mg/kg, 16 h). MicroRNA (miRNA) expression and the underlying molecular mechanisms were assessed using transfection technique and western blotting.
  
  
  CONCLUSIONS
  Curcumin efficiently inhibited LPS-induced cytokines (TNF-α, IL-6) and microRNA-155 (miR-155) expression (p < 0.05) without affecting the normally growth of Raw264.7 and THP-1 cells (IC5021.8 and 22.3 μM at 48 h, respectively). Moreover, the levels of cytokines were suppressed by curcumin in miR-155 mimics transfected cells (p < 0.05). A blockade of PI3K/AKT signalling pathways resulted in a decreased level of miR-155 (p < 0.05). Curcumin effectively protected mice from sepsis as evidenced by decreasing histological damage, reducing AST (352.0 vs 279.3 U/L), BUN (14.8 vs 10.8 mmol/L) levels and the proportion of macrophages in spleen (31.1% vs 13.5%). MicroRNA-155 level and cytokines were also reduced in curcumin-treated mice (p < 0.05).
  
  
  CONCLUSIONS
  Curcumin's ability to suppress LPS-induced inflammatory response may be due to the inhibition of miR-155.
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Ma
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yue
authors.affiliation: b The Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology , Medical School, Nanjing University , Nanjing , PR China.|c Jiangsu Key Laboratory of Molecular Medicine , Medical School, Nanjing University , Nanjing , PR China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D003474:Curcumin
keywords: AKT; Phosphoinositide 3-kinase (PI3K); inflammation; p85α; sepsis