First Author | Zhang P | Year | 2019 |
Journal | Yonsei Med J | Volume | 60 |
Issue | 11 | Pages | 1093-1102 |
PubMed ID | 31637892 | Mgi Jnum | J:287887 |
Mgi Id | MGI:6416019 | Doi | 10.3349/ymj.2019.60.11.1093 |
Citation | Zhang P, et al. (2019) Inhibition of miRNA-222-3p Relieves Staphylococcal Enterotoxin B-Induced Liver Inflammatory Injury by Upregulating Suppressors of Cytokine Signaling 1. Yonsei Med J 60(11):1093-1102 |
abstractText | 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-gamma), tumor necrosis factor-alpha (TNF-alpha), 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-gamma, TNF-alpha, 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-gamma, TNF-alpha, 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. |