Extracellular vesicles containing miR-146a attenuate experimental colitis bytargeting TRAF6 and IRAK1

Accumulating evidence indicates that microRNA-146a (miR-146a), a well-known anti-inflammatory miRNA,acts as a negative feedback regulator of the innate immune response, but its role in modulation of inflammatorybowel disease (IBD) remains unclear and the issue related to the stability of exogenous miR-146a in blood is upin the air. In this study, extracellular vesicles (EVs) from cultured medium of bone-marrow mesenchymal stemcells (BMSCs) transfected with recombinant lentiviruses can serve as a stable delivery system and overexpressmiR-146a, which significantly inhibited TNF receptor–associated factor 6 (TRAF6) and IL-1 receptor-associatedkinase 1 (IRAK1) expression in TNBS-induced colitis of rats. Moreover, the increased phosphorylation levels ofNF-κB p65 and IκBαwere down-regulated by the administration of EVs containing miR-146a. Coupled with theassociated influence of over-expressed miR-146a on phosphorylated proteins above, the production of in-flammation factors such as tumor necrosis factor-α(TNF-α), Interleukin-6 (IL-6) and Interleukin-1βis apparentlysuppressed by this non-coding RNA. Collectively, these data elucidated that EVs containing miR-146a amelio-rates experimental colitis caused 2,4,6‑trinitrobenzenesulfonic acid (TNBS) by targeting TRAF6 and IRAK1