Int Immunopharmacol . 2016 Nov;40:339-346. doi: 10.1016/j.intimp.2016.09.011. Epub 2016 Sep 24.

Fine-tuning the expression of microRNA-155 controls acetaminophen-induced liver inflammation

Kai Yuan  1 Xue Zhang  2 Lei Lv  3 Jiwei Zhang  1 Wei Liang  1 Peng Wang  4

Affiliations

  • 1 Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
  • 2 Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, China.
  • 3 Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
  • 4 Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China. Electronic address: wangpengrenji@163.com.

Abstract

Treatment of acetaminophen (APAP) in overdose can cause a potentially serious and fatal liver injury. MicroRNA-155 (miR-155), a multifunctional microRNA, is known to mediate inflammatory responses via regulating various target genes. In this study, we aimed to study the role of miR-155 in APAP-induced liver injury, using miR-155-/- mice and miR-155 in vivo intervention. We noted that miR-155 expression was significantly increased in liver and blood after APAP treatment. Knockout of miR-155 deteriorated APAP-induced liver damage, with the elevated serum levels of AST and ALT. The levels of various inflammatory mediators, such as TNF-α and IL-6, were markedly augmented in livers in the absence of miR-155. Moreover, miR-155 deficiency aberrantly activated NF-kappa-B signaling via enhancing p65 and IKKε expression. Finally, in vivo administration of miR-155 agomir attenuated APAP-induced liver damage, reduced the serum levels of AST and ALT, and dampened the NF-kB signaling. In conclusion, our data demonstrated that miR-155 protects the mice against APAP-induced liver damage via mediating NF-KB signaling pathway, suggesting that miR-155 might be a potential pharmaceutic target for treatment of APAP-induced liver inflammation.

Keywords: Acetaminophen; Acute liver damage; Inflammation; MicroRNA-155.

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