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

Overview

Journal Yonsei Med J

Specialty General Medicine

Date 2019 Oct 23

PMID 31637892

Citations 4

Authors

Peng Zhang

Jingda Yu

Yifang Gui

Cui Sun

Weiping Han

Affiliations

Soon will be listed here.

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.

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References

Zhang H, Zhao Z, Pang X, Yang J, Yu H, Zhang Y . Genistein Protects Against Ox-LDL-Induced Inflammation Through MicroRNA-155/SOCS1-Mediated Repression of NF-ĸB Signaling Pathway in HUVECs. Inflammation. 2017; 40(4):1450-1459. DOI: 10.1007/s10753-017-0588-3. View

Kadhim S, Singh N, Zumbrun E, Cui T, Chatterjee S, Hofseth L . Resveratrol-Mediated Attenuation of Enterotoxin B-Induced Acute Liver Injury Is Associated With Regulation of microRNA and Induction of Myeloid-Derived Suppressor Cells. Front Microbiol. 2019; 9:2910. PMC: 6304356. DOI: 10.3389/fmicb.2018.02910. View

Mann M, Mehta A, Zhao J, Lee K, Marinov G, Garcia-Flores Y . An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses. Nat Commun. 2017; 8(1):851. PMC: 5636846. DOI: 10.1038/s41467-017-00972-z. View

Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K . MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 2012; 61(11):1600-9. DOI: 10.1136/gutjnl-2011-300717. View

Ren J, Ying R, Cheng Y, Wang L, El Gazzar M, Li G . HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development. J Viral Hepat. 2016; 23(10):755-66. PMC: 5028233. DOI: 10.1111/jvh.12537. View

Inagaki-Ohara K, Kondo T, Ito M, Yoshimura A . SOCS, inflammation, and cancer. JAKSTAT. 2013; 2(3):e24053. PMC: 3772102. DOI: 10.4161/jkst.24053. View

Rieder S, Nagarkatti P, Nagarkatti M . CD1d-independent activation of invariant natural killer T cells by staphylococcal enterotoxin B through major histocompatibility complex class II/T cell receptor interaction results in acute lung injury. Infect Immun. 2011; 79(8):3141-8. PMC: 3147567. DOI: 10.1128/IAI.00177-11. View

Fiorino S, Bacchi-Reggiani M, Visani M, Acquaviva G, Fornelli A, Masetti M . MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma. World J Gastroenterol. 2016; 22(15):3907-36. PMC: 4823242. DOI: 10.3748/wjg.v22.i15.3907. View

Yin T, Tong S, Xie Y . Cyclosporin A protects Balb/c mice from liver damage induced by superan tigen SEB and D-GalN. World J Gastroenterol. 2002; 5(3):209-212. PMC: 4688470. DOI: 10.3748/wjg.v5.i3.209. View

10.

Pinchuk I, Beswick E, Reyes V . Staphylococcal enterotoxins. Toxins (Basel). 2011; 2(8):2177-97. PMC: 3153290. DOI: 10.3390/toxins2082177. View

11.

Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B . miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci U S A. 2009; 107(1):264-9. PMC: 2806773. DOI: 10.1073/pnas.0907904107. View

12.

Motawi T, Sadik N, Shaker O, Ghaleb M . Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer. Tumour Biol. 2016; 37(7):9865-74. DOI: 10.1007/s13277-016-4884-6. View

13.

Tan L, Jiang W, Lu A, Cai H, Kong L . miR-155 Aggravates Liver Ischemia/reperfusion Injury by Suppressing SOCS1 in Mice. Transplant Proc. 2018; 50(10):3831-3839. DOI: 10.1016/j.transproceed.2018.08.060. View

14.

de Araujo Junior R, Garcia V, Leitao R, Brito G, Miguel E, Guedes P . Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells. PLoS One. 2016; 11(2):e0148868. PMC: 4758650. DOI: 10.1371/journal.pone.0148868. View

15.

Elliott D, Nagarkatti M, Nagarkatti P . 3,39-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B–Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells. J Pharmacol Exp Ther. 2016; 357(1):177-87. PMC: 4809322. DOI: 10.1124/jpet.115.226563. View

16.

Li Y, Liang C, Ma H, Zhao Q, Lu Y, Xiang Z . miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer. Molecules. 2014; 19(6):7122-37. PMC: 6271560. DOI: 10.3390/molecules19067122. View

17.

Mirzaei H, Sahebkar A, Mohammadi M, Yari R, Salehi H, Jafari M . Circulating microRNAs in Hepatocellular Carcinoma: Potential Diagnostic and Prognostic Biomarkers. Curr Pharm Des. 2016; 22(34):5257-5269. DOI: 10.2174/1381612822666160303110838. View

18.

Plaza R, Vidal S, Rodriguez-Sanchez J, Juarez C . Implication of STAT1 and STAT3 transcription factors in the response to superantigens. Cytokine. 2003; 25(1):1-10. DOI: 10.1016/j.cyto.2003.09.006. View

19.

Qi P, Cheng S, Wang H, Li N, Chen Y, Gao C . Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. PLoS One. 2011; 6(12):e28486. PMC: 3234251. DOI: 10.1371/journal.pone.0028486. View

20.

Rao R, Rieder S, Nagarkatti P, Nagarkatti M . Staphylococcal enterotoxin B-induced microRNA-155 targets SOCS1 to promote acute inflammatory lung injury. Infect Immun. 2014; 82(7):2971-9. PMC: 4097622. DOI: 10.1128/IAI.01666-14. View