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

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.