Inhibition of miRNA-222-3p Relieves Staphylococcal Enterotoxin B-Induced Liver Inflammatory Injury by Upregulating Suppressors of Cytokine Signaling 1
10.3349/ymj.2019.60.11.1093
- Author:
Peng ZHANG
1
;
Jingda YU
;
Yifang GUI
;
Cui SUN
;
Weiping HAN
Author Information
1. Department of Clinical Laboratory, the Third People's Hospital of Dalian, Dalian, China.
- Publication Type:Original Article
- Keywords:
miR-222-3p;
SEB;
inflammatory cytokine;
liver injury
- MeSH:
Alanine Transaminase;
Animals;
Aspartate Aminotransferases;
Blotting, Western;
Cytokines;
Down-Regulation;
Enterotoxins;
Enzyme-Linked Immunosorbent Assay;
Interferon-gamma;
Interleukin-2;
Interleukin-6;
Liver;
Luciferases;
Lung Injury;
Mice;
Polymerase Chain Reaction;
Tumor Necrosis Factor-alpha;
Up-Regulation
- From:Yonsei Medical Journal
2019;60(11):1093-1102
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) was implicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-induced liver injury. MATERIALS AND METHODS: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-time quantitative PCR and western blot. Liver injury was determined by levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory cytokines, numbers of infiltrating mononuclear cells using AST/ALT assay kit, enzyme-linked immunosorbent assay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 was predicted on targetScan software, and confirmed by luciferase reporter assay. RESULTS: SEB induced liver injury in D-galactosamine (D-gal)-sensitized mice, as demonstrated by increased serum levels of AST and ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, and promoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulated in SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviated liver injury accompanied with SOCS1 upregulation. Besides, splenocytes under SEB challenge released less INF-γ, TNF-α, IL-6, and IL-2 during miR-222-3p knockdown. Mechanically, SOCS1 was targeted and downregulated by miR-222-3p. Upregulation of SOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block the suppressive role of miR-222-3p knockdown in SEB-induced splenocytes. CONCLUSION: Inhibition of miR-222-3p relieves SEB-induced liver inflammatory injury by upregulating SOCS1, thereby providing the first evidence of miR-222-3p in SEB-induced liver injury.
