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        Inhibition of miRNA-222-3p Relieves Staphylococcal Enterotoxin B-Induced Liver Inflammatory Injury by Upregulating Suppressors of Cytokine Signaling 1

        Peng Zhang,Jingda Yu,Yifang Gui,Cui Sun,Weiping Han 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.11

        Purpose: Staphylococcal enterotoxin B (SEB) has been well-documented to induce liver injury. miRNA-222-3p (miR-222-3p) wasimplicated in SEB-induced lung injury and several liver injuries. This study aimed to explore the role of miR-222-3p in SEB-inducedliver injury. Materials and Methods: Expression of miR-222-3p and suppressors of cytokine signaling 1 (SOCS1) was detected using real-timequantitative 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 immunosorbentassay (ELISA), and hematoxylin-eosin staining, respectively. Target binding between miR-222-3p and SOCS1 waspredicted 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 ASTand ALT, elevated release of interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-2, andpromoted infiltrating immune cells into liver. Expression of miR-222-3p was dramatically upregulated, and SOCS1 was downregulatedin SEB-induced liver injury both in mice and splenocytes. Moreover, miR-222-3p knockout (KO) mice exhibited alleviatedliver 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 ofSOCS1 attenuated INF-γ, TNF-α, IL-6, and IL-2 release in SEB-induced splenocytes; downregulation of SOCS1 could block thesuppressive 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 providingthe first evidence of miR-222-3p in SEB-induced liver injury.

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