Staphylococcal enterotoxin B (SEB)-induced miR-155 targets SOCS-1 to promote acute inflammatory lung injury. (IRM7P.481)

Abstract

Abstract Staphylococcal enterotoxin B (SEB) initiates an exaggerated inflammatory response characterized by immune cell infiltration, the release of inflammatory cytokines and tissue damage. However, the role of microRNAs (miR) associated with the damaging effects of SEB have not yet been delineated. In this study, we show that inhalation exposure to SEB results in acute inflammatory lung injury accompanied by altered miR expression profile in lung infiltrating cells. Amongst the miRNA that were significantly elevated, miR-155 is the most over-expressed. In contrast, miR-155-/- mice were protected from SEB-mediated inflammation. Interestingly, there was a positive correlation between miR-155 levels and IFN-γ secretion, suggesting a functional link between SEB-induced miR-155 and pro-inflammatory cytokine IFN-γ. Through the use of bioinformatics tools, suppressor of cytokine signaling -1 (SOCS1), a negative regulator of IFN-γ, was identified as a potential target of miR-155. While miR-155-/- mice displayed increased SOCS1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-γ levels. Additionally, the inhibition of miR-155 and IFN-γ resulted in restored SOCS1 expression. Our data, therefore, confirm an important role of miR-155 in facilitating SEB-mediated inflammation and proposes that miR-155 may be an important target in the treatment of acute lung inflammation.