MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with sepsis.
In the miR-146a agonist group, levels of myocardial injury markers were lower than those in the sepsis model group, but were higher in the miR-146a inhibition group.
Sepsis was induced in mice via cecal ligation and puncture (CLP) and an intravenous injection of a complex of miR-146a-expressing plasmid and polyethyleneimine.
In conclusion, our results demonstrated that the overexpression of miR-146a mitigates myocardial injury by negatively regulating NF-<i>κ</i>B activation and inflammatory cytokine production via targeting ErbB4 in LPS-induced sepsis.
Therefore, we prove that miR-146a acts as an inhibitor of inflammation by targeting Notch1 in macrophage, therefore protects mice from organ damage in sepsis.
Our results thus suggest that miR-146a is a mediator of IVIg effects in inflammatory disorders, point to an important role for miR-146a in the control of inflammation during sepsis and highlight a new mechanism by which IVIg exerts its anti-inflammatory effects in sepsis.
Collectively, our results identify miR-146a as a potent inhibitor of Th1-cell differentiation in human T cells and suggest that dysregulation of miR-146a contributes to the pathogenesis of sepsis.
Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls).