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Extracellular vesicles containing miR-146a attenuate experimental colitis by targeting TRAF6 and IRAK1.

Abstract：

: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 inflammatory bowel disease (IBD) remains unclear and the issue related to the stability of exogenous miR-146a in blood is up in the air. In this study, extracellular vesicles (EVs) from cultured medium of bone-marrow mesenchymal stem cells (BMSCs) transfected with recombinant lentiviruses can serve as a stable delivery system and overexpress miR-146a, which significantly inhibited TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) expression in TNBS-induced colitis of rats. Moreover, the increased phosphorylation levels of NF-κB p65 and IκBα were down-regulated by the administration of EVs containing miR-146a. Coupled with the associated influence of over-expressed miR-146a on phosphorylated proteins above, the production of inflammation factors such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β is apparently suppressed by this non-coding RNA. Collectively, these data elucidated that EVs containing miR-146a ameliorates experimental colitis caused 2,4,6‑trinitrobenzenesulfonic acid (TNBS) by targeting TRAF6 and IRAK1.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Wu H,Fan H,Shou Z,Xu M,Chen Q,Ai C,Dong Y,Liu Y,Nan Z,Wang Y,Yu T,Liu X

doi

10.1016/j.intimp.2018.12.043

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

204-212

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)30527-7

journal_volume

68

pub_type

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