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MiR-222 inhibition alleviates Staphylococcal Enterotoxin B-induced inflammatory acute lung injury by targeting Foxo3

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Abstract

Acute lung injury (ALI) is a common acute and severe disease in clinical practice. Staphylococcal Enterotoxin B (SEB) is a superantigen that can cause inflammatory ALI. MiR-222 has been demonstrated to be upregulated in SEB-induced inflammatory ALI, but its exact roles and functions remain ill-defined. In this study, SEB exposure led to inflammatory ALI and high expression of miR-222 in model mice and lung infiltrating mononuclear cells, but the inflammatory response and high expression of miR-222 were restored in miR-222-/- mice. Moreover, we investigated the roles of miR-222 in vitro and observed that the concentrations of inflammatory cytokines and the expression of miR-222 were all elevated in SEB-activated splenocytes and miR-222 inhibition reversed the effects. Foxo3 was confirmed as a direct target of miR-222. Interestingly, SEB exposure led to a decrease of Foxo3 expression, and Foxo3 knockdown partially reversed the promotion of Foxo3 and the inhibition of inflammatory cytokines induced by miR-222 inhibitor in SEB-activated splenocytes. Our data indicated that miR-222 inhibition could alleviate SEB-induced inflammatory ALI by directly targeting Foxo3, shedding light on the potential therapeutic of miR-222 for SEB-induced inflammation in the lung.

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Authors and Affiliations

  1. Department of Infectious Disease, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, China

    Liang Chen

  2. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

    Jun Chen

  3. Department of Pulmonary and Critical Care Medicine, Shanghai General Hospital, Shanghai, China

    Guogang Xie

  4. Department of Chronic Disease and Infectious Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China

    Limei Zhu

Authors
  1. Liang Chen
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  2. Jun Chen
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  3. Guogang Xie
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  4. Limei Zhu
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Correspondence to Liang Chen.

Additional information

Communicated by Dipankar Nandi

Corresponding editor: Dipankar Nandi

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Chen, L., Chen, J., Xie, G. et al. MiR-222 inhibition alleviates Staphylococcal Enterotoxin B-induced inflammatory acute lung injury by targeting Foxo3. J Biosci 45, 65 (2020). https://doi.org/10.1007/s12038-020-00037-2

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  • DOI: https://doi.org/10.1007/s12038-020-00037-2

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