Expression of microRNA-146a in myeloid derived suppressor cells and its significance / 军事医学

ABSTRACT

Objective To compare the phenotype of myeloid derived suppressor cells (MDSCs) separated from the bone marrow of mice 3 d and 7 d after cecal ligation and puncture ( CLP) and to elucidate its potential role in the accumulation and immuno-function of MDSCs by determining the expression of microRNA-146a(miR-146a)in order to explore the effect of miR-146 a on immonosuppression of MDSCs in sepsis .Methods A septic model was prepareol by CLP in adult male C57BL/6J mice.MDSCs(expressing cell-surface CD11b and GR-1 antigens )from bone marrow were harvested 3 and 7 days after CLP and were separated with magnetic bead sorting technique .Then,cytokines secretion and arginase-I activity were detected and the T cell proliferation in vitro and the expression of miR-146a of MDSCs (3 d and 7 d after CLP)were observed.Results MDSCs secreted mostly such promoting inflammatory factors as TNF-α, IL-6 3 days after CLP, but 7 days after CLP , they primarily secreted IL-10 and TGF-βwhich were anti-inflammatory factors . MDSCs had potent immunosuppressive properties by increasing T cell suppression in a late anti-inflammatory phase ( CLP3 d vs CLP7 d, P<0.05).In the meantime,miR-146a of the MDSCs in bone marrow was overexpressed in septic mice at 7 days(P<0.05). Moreover,the expression of miR-146a of the MDSCs in bone marrow of septic mice was higher at 7 days than at 3 days after CLP(P<0.05).Conclusion The data indicate that the phenotype of MDSCs evolves through early pro -inflammatory phase into the late anti-inflammatory phase .MDSCs have potent immunosuppressive properties in the late phase of sepsis . miR-146 a might play a crucial role in the regulation of immunosuppressive activity of MDSCs in late sepsis .